Affinage

MSX1

Homeobox protein MSX-1 · UniProt P28360

Length
303 aa
Mass
31.5 kDa
Annotated
2026-04-28
100 papers in source corpus 32 papers cited in narrative 32 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MSX1 is a homeodomain transcription factor that functions as a key mediator of BMP4 and Wnt signaling to maintain progenitor cell states and regulate epithelial–mesenchymal interactions during craniofacial, tooth, limb, and neural crest development. MSX1 represses differentiation-promoting genes such as MyoD by binding target enhancers (TAAT core motif), recruiting linker histone H1b and chromatin-modifying cofactors (EZH2, HDACs), and being targeted to the nuclear periphery through interaction with PIAS1 (PMID:7664340, PMID:15192231, PMID:16600910, PMID:25101640). In dental mesenchyme, MSX1 cooperates physically with Pax9 and antagonizes Osr2 and Tbx2 to sustain Bmp4 expression and suppress Wnt antagonists (Dkk2, Sfrp2), and its activity is modulated by CDK1 phosphorylation at Ser136 to drive FGF9/18–ERK proliferative signaling (PMID:16651263, PMID:23720046, PMID:27713059, PMID:33080014). Loss-of-function mutations in MSX1—including the homeodomain missense Arg31Pro—cause autosomal dominant tooth agenesis in humans, and Msx1-null mice exhibit cleft palate, arrested tooth development, and alveolar bone deficiency (PMID:8696335, PMID:7914451).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1992 High

    The first functional role for MSX1 was established when forced expression in committed myoblasts blocked terminal differentiation and reduced MyoD levels, revealing MSX1 as an inhibitor of cellular differentiation programs.

    Evidence Overexpression in myogenic cell lines with differentiation readout

    PMID:1360150

    Open questions at the time
    • Mechanism of MyoD repression (direct or indirect) was unknown
    • No in vivo loss-of-function data yet
  2. 1994 High

    Gene knockout resolved MSX1's organismal requirement: Msx1-null mice displayed cleft palate, tooth arrest at the bud stage, and alveolar bone deficiency, establishing MSX1 as essential for craniofacial epithelial–mesenchymal interactions.

    Evidence Msx1 knockout mouse, histological phenotypic analysis

    PMID:7914451

    Open questions at the time
    • Whether the defect was cell-autonomous or non-cell-autonomous was not resolved
    • Downstream molecular targets were not identified
  3. 1995 High

    MSX1 was shown to directly bind the MyoD core enhancer and repress MyoD transcription, establishing the first direct transcriptional target and confirming MSX1 as a DNA-binding transcriptional repressor.

    Evidence Chromosome transfer hybrids, gel-shift, reporter assays, antisense rescue

    PMID:7664340

    Open questions at the time
    • Chromatin-level mechanism of repression not yet defined
    • DNA-binding specificity determinants unknown
  4. 1996 High

    Two advances defined MSX1's DNA recognition and disease relevance: in vitro assays showed MSX1 binds a TAAT core motif and represses transcription through N-terminal domains outside the homeodomain, while a human Arg31Pro homeodomain mutation was found to cause autosomal dominant tooth agenesis, linking DNA binding to in vivo function.

    Evidence In vitro binding/mutagenesis plus human genetic linkage and sequencing

    PMID:8696335 PMID:8861098

    Open questions at the time
    • How MSX1 selects specific TAAT sites genome-wide was unexplained
    • Functional consequence of Arg31Pro on protein activity not directly tested
  5. 1997 High

    Epistasis experiments in Xenopus placed MSX1 as an immediate-early effector downstream of BMP4, rescuing neuralization caused by dominant-negative BMP receptor and inducing epidermal fate, thereby positioning MSX1 within BMP signaling.

    Evidence Xenopus ectodermal explants, overexpression, dominant-negative BMP receptor epistasis

    PMID:9272945

    Open questions at the time
    • Whether MSX1 is a direct BMP transcriptional target or requires intermediaries was unresolved
    • Relationship between BMP-downstream repression and MyoD pathway unclear
  6. 2000 High

    Tissue recombination and BMP4 rescue experiments demonstrated that MSX1 functions non-cell-autonomously in dental mesenchyme upstream of BMP4, with exogenous BMP4 fully rescuing tooth morphogenesis in Msx1-null explants through the cap stage.

    Evidence Wild-type/Msx1-null epithelial–mesenchymal tissue recombination, kidney capsule grafting with BMP4

    PMID:11023873

    Open questions at the time
    • How MSX1 regulates Bmp4 transcription was not defined
    • Whether additional signals besides BMP4 are required downstream was not tested
  7. 2001 Medium

    An endogenous antisense RNA (Msx1-AS) was identified that inversely correlates with MSX1 protein in differentiated cells, suggesting post-transcriptional regulation of MSX1, and Msx1 was shown to repress Cbfa1/Runx2, linking it to osteogenic control.

    Evidence In situ hybridization, overexpression in odontoblastic cells, primer extension

    PMID:11390985

    Open questions at the time
    • Functional role of antisense RNA not directly tested by loss-of-function
    • Mechanism of Cbfa1 repression not established
  8. 2003 High

    Multiple studies converged to show MSX1 regulates proliferation and bone/regeneration pathways: MSX1 represses the CDK inhibitor p19(INK4d) in cranial neural crest–derived dental mesenchyme to maintain proliferation, and MSX1/BMP4 epistasis controls both digit regeneration and alveolar bone formation through Dlx5 and Cbfa1.

    Evidence Msx1 KO with lineage tracing, explant rescue of p19INK4d; Msx1 KO digit regeneration with BMP4 rescue; in situ for Dlx5/Cbfa1 in KO and transgenic mice

    PMID:12941628 PMID:12944425 PMID:14654219

    Open questions at the time
    • Whether MSX1 directly binds p19INK4d regulatory regions was not shown
    • Integration of proliferation control with differentiation repression unclear
  9. 2004 High

    A chromatin-level mechanism for MSX1-mediated repression was established: MSX1 physically interacts with linker histone H1b and together they bind the MyoD core enhancer to induce a repressive chromatin state, inhibiting myogenesis in vitro and in Xenopus.

    Evidence Co-immunoprecipitation, chromatin binding assay, myoblast differentiation assay, Xenopus animal cap assay

    PMID:15192231

    Open questions at the time
    • Which other chromatin-modifying enzymes cooperate with MSX1–H1b was unknown
    • Genome-wide scope of H1b-dependent repression not tested
  10. 2004 High

    MSX1 was shown to be required for myofiber dedifferentiation (cellularization) during salamander limb regeneration, extending its role as a dedifferentiation factor beyond embryonic contexts.

    Evidence Morpholino knockdown in isolated salamander myofibers, lineage tracing, time-lapse microscopy

    PMID:15314647

    Open questions at the time
    • Downstream targets of MSX1 in regeneration not identified
    • Whether this mechanism operates in mammalian regeneration contexts was unknown
  11. 2005 High

    MSX1 was placed upstream of Pax3 in neural crest induction, acting cell-autonomously downstream of FGF8 to induce Pax3 and ZicR1 expression during Xenopus neural crest specification.

    Evidence Morpholino knockdown and overexpression epistasis in Xenopus embryos

    PMID:15691759

    Open questions at the time
    • Whether MSX1 directly activates Pax3 transcription was not tested
    • Mechanism by which FGF8 induces MSX1 unknown
  12. 2006 High

    Two key protein partners of MSX1 in tooth development were identified: PIAS1 confers DNA-binding specificity and targets MSX1 to the nuclear periphery (independently of sumoylation), while Pax9 physically interacts with MSX1 and synergistically transactivates the Bmp4 promoter for bud-to-cap transition.

    Evidence Co-IP, ChIP, siRNA, subnuclear imaging for PIAS1; Co-IP, GST pulldown, promoter-reporter for Pax9; compound mutant mice

    PMID:15721141 PMID:16600910 PMID:16651263

    Open questions at the time
    • How PIAS1 mechanistically alters MSX1 DNA selectivity at the structural level was unresolved
    • Which Pax9–MSX1 interaction surfaces mediate synergistic transactivation was not mapped
  13. 2011 High

    Osr2 was identified as a stable MSX1-interacting protein that antagonizes MSX1 in the odontogenic field; genetic deletion of Osr2 rescued molar development in Msx1-null mice, establishing an antagonistic regulatory circuit.

    Evidence Co-immunoprecipitation, Osr2/Msx1 compound mutant mice with genetic rescue

    PMID:21420399

    Open questions at the time
    • Whether Osr2 blocks MSX1 DNA binding or cofactor recruitment was not distinguished
    • Spatial determinants of Osr2–MSX1 antagonism in the tooth field not mapped
  14. 2013 High

    Tbx2 was shown to physically interact with MSX1 and antagonize its activation of the Bmp4 promoter; partial Tbx2 loss rescued Msx1-null tooth arrest, revealing a dosage-sensitive antagonistic network controlling enamel knot formation.

    Evidence Co-IP in C3H10T1/2 cells, Tbx2/Msx1 compound mutant mice, siRNA knockdown

    PMID:23720046

    Open questions at the time
    • Whether Tbx2 competes with Pax9 for MSX1 binding was not tested
    • Temporal dynamics of Tbx2–MSX1 interaction during morphogenesis not resolved
  15. 2014 High

    MSX1 was shown to function as a transcriptional activator at the Atoh1 enhancer—not solely a repressor—directly binding and activating Atoh1 to specify dI1 interneurons in the dorsal spinal cord, and homeodomain mutations (T174I, L205R) were shown to abolish both DNA binding and EZH2 interaction.

    Evidence In vitro transcription assay, ChIP, Msx1/Msx2 double KO mice; EMSA, Co-IP with EZH2, reporter assay

    PMID:24715462 PMID:25101640

    Open questions at the time
    • How MSX1 switches between activator and repressor modes on different targets was not explained
    • Genome-wide catalog of MSX1-activated versus repressed targets absent
  16. 2016 High

    MSX1 was shown to maintain canonical Wnt signaling in the dental mesenchyme by repressing Wnt antagonists Dkk2 and Sfrp2; pharmacological Wnt activation or genetic removal of these antagonists rescued tooth morphogenesis in Msx1-null mice, revealing a previously unrecognized Wnt-regulatory function.

    Evidence RNA-seq of tooth mesenchyme, compound mutant mice, in utero LiCl treatment

    PMID:27713059

    Open questions at the time
    • Whether MSX1 directly binds Dkk2/Sfrp2 regulatory regions was not shown
    • Relative contributions of BMP4 versus Wnt rescue in tooth development not quantified
  17. 2020 High

    Post-translational regulation of MSX1 was defined: CDK1-mediated phosphorylation at Ser136 is required for MSX1 to bind Fgf9 and Fgf18 promoters and upregulate their expression, activating ERK1/2 signaling to drive mesenchymal and myoblast proliferation during limb development.

    Evidence Phospho-site mutagenesis, ChIP on Fgf9/18 promoters, FGF antibody neutralization, conditional Msx1/2 KO, Western blot for pERK1/2

    PMID:33080014

    Open questions at the time
    • Whether CDK1 phosphorylation affects MSX1 interactions with H1b, PIAS1, or EZH2 was not tested
    • Other phosphorylation sites or kinases regulating MSX1 not surveyed

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how MSX1 switches between transcriptional repression (e.g., MyoD) and activation (e.g., Atoh1, Bmp4, Fgf9/18) at different genomic loci, and no genome-wide binding profile (ChIP-seq) has been reported to define its full target repertoire across developmental contexts.
  • No ChIP-seq or CUT&RUN map for MSX1 in any tissue
  • Structural basis for cofactor-dependent switching between activation and repression unknown
  • How MSX1 antisense RNA regulation integrates with protein-level mechanisms in vivo is untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 10 GO:0003677 DNA binding 5 GO:0042393 histone binding 1
Localization
GO:0005634 nucleus 4 GO:0005635 nuclear envelope 2
Pathway
R-HSA-1266738 Developmental Biology 13 R-HSA-74160 Gene expression (Transcription) 7 R-HSA-162582 Signal Transduction 6 R-HSA-4839726 Chromatin organization 2
Partners
EZH2H1B (HIST1H1B)OSR2PAX3PAX9PIAS1TBX2

Evidence

Reading pass · 32 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1994 Msx1 knockout mice exhibit cleft secondary palate, failure of tooth development at the bud stage, and deficiencies of alveolar bone, demonstrating a critical role for Msx1 in mediating epithelial-mesenchymal interactions during craniofacial bone and tooth development. Knockout mouse (loss-of-function), histological and phenotypic analysis Nature genetics High 7914451
1992 Forced expression of Hox-7.1 (Msx1) in determined myogenic cells blocks terminal differentiation, decreases steady-state levels of MyoD1, and induces a transformed phenotype, demonstrating that Msx1 inhibits myogenic differentiation. Transfection/overexpression in myogenic cell line, phenotypic readout of differentiation block Nature High 1360150
1996 A missense mutation Arg31Pro in the MSX1 homeodomain causes autosomal dominant familial tooth agenesis; Arg31 is a conserved residue that interacts with the ribose-phosphate backbone of target DNA, indicating DNA binding is essential for MSX1 function in tooth development. Genetic linkage analysis, DNA sequencing, functional inference from residue conservation Nature genetics Medium 8696335
1995 MSX1 protein binds directly to the MyoD core enhancer (CE) and represses MyoD transcription; MSX1 is expressed from chromosome 4 in fibroblast-10T1/2 hybrids and antisense MSX1 relieves this repression, establishing MyoD as a direct transcriptional target. Chromosome transfer hybrid assay, reporter assays, DNA binding (gel shift/ChIP inference), antisense rescue Cell High 7664340
1996 MSX-1 and MSX-2 both bind a common consensus DNA site (TAAT core) and both function as transcriptional repressors independently of their consensus DNA binding sites; MSX-1 is a more potent repressor than MSX-2, with differences mapping to N-terminal regions outside the homeodomain. In vitro DNA binding assays, transcriptional reporter assays, deletion mutagenesis Mechanisms of development High 8861098
1997 Xenopus msx1 acts as an immediate-early mediator of BMP4 signaling: overexpression of msx1 induces epidermal fate in dissociated ectoderm and rescues neuralization imposed by dominant-negative BMP receptor, placing msx1 downstream of BMP4 in epidermal induction. Overexpression in Xenopus embryos, ectodermal explant assays, dominant-negative BMP receptor epistasis Development High 9272945
2000 Msx1 is required in the dental mesenchyme (not epithelium) for tooth formation; BMP4 added exogenously to Msx1-deficient tooth germs fully rescues tooth development through the cap stage to enamel/dentin formation, establishing that Msx1 functions non-cell-autonomously upstream of BMP4 in the dental mesenchyme. Tissue recombination between wild-type and Msx1 mutant dental epithelium/mesenchyme; kidney capsule grafting with BMP4 rescue Development High 11023873
2003 Msx1 regulates BMP4 production during digit regeneration; Msx1 null mice show downregulated Bmp4 and regeneration failure that is rescued dose-dependently by exogenous BMP4, placing Msx1 upstream of Bmp4 in the digit regeneration pathway. Msx1 knockout mice, organ culture digit regeneration assay, exogenous BMP4 rescue, Noggin inhibition Development High 12944425
2004 Msx1 interacts physically with histone H1b (a specific linker histone isoform); together they bind the MyoD Core Enhancer Region (CER) and induce repressed chromatin, cooperatively inhibiting muscle differentiation in myoblast cells and in Xenopus animal caps. Co-immunoprecipitation, chromatin binding assays, cell culture differentiation assays, Xenopus animal cap assay Science High 15192231
2005 In Xenopus, Msx1 and Pax3 are both required for neural crest formation; Msx1 acts upstream of Pax3 (inducing Pax3 and ZicR1 cell-autonomously), and FGF8 promotes neural crest through both Msx1 and Pax3 activities, while WNTs act through Pax3 activity. Morpholino knockdown, overexpression, epistasis analysis in Xenopus embryos Developmental cell High 15691759
2006 PIAS1 confers DNA-binding specificity on Msx1 by regulating its subnuclear localization to the nuclear periphery; PIAS1 interaction (not sumoylation) is required for Msx1 to selectively bind the MyoD CER and repress myogenic genes. PIAS1 retention of Msx1 at the nuclear periphery co-localizes with peripherally located MyoD and Myf5 target genes. Co-IP, ChIP, siRNA knockdown, subnuclear localization imaging (immunofluorescence), myoblast differentiation assay Genes & development High 16600910
2006 Pax9 physically interacts with Msx1 protein (demonstrated by co-IP and GST pulldown) and directly regulates Msx1 expression; together Pax9 and Msx1 synergistically transactivate the Bmp4 promoter, placing them in a cooperative pathway essential for the bud-to-cap stage transition in tooth development. Co-immunoprecipitation, GST pulldown, promoter-reporter transactivation assays, expression analysis in Pax9 mutant mice Journal of Biological Chemistry High 16651263
2001 Msx3 represses the Msx1 promoter by: (1) interacting with CBP/p300 and inhibiting their HAT activity, and (2) recruiting HDAC1 in a separate complex. Both mechanisms converge on chromatin-level repression of Msx1 transcription. Co-immunoprecipitation, HAT activity assay, HDAC inhibitor (trichostatin A) rescue, transcriptional reporter assay in C2C12 cells Biochemical Journal High 11115394
2003 Msx1 regulates cranial neural crest (CNC)-derived dental mesenchyme proliferation by controlling the CDK inhibitor p19(INK4d); in Msx1 null mutants, CNC-derived dental mesenchyme is deficient due to elevated p19(INK4d) activity. Attenuation of p19(INK4d) in Msx1 null mandibular explants restores mitotic activity. Genetic lineage tracing (two-component Cre system), cell proliferation assays, mandibular explant culture with p19(INK4d) attenuation Developmental biology High 12941628
2004 Msx1 expression in salamander myofibers is required for cellularization (dedifferentiation); morpholino antisense knockdown of Msx1 in single isolated myofibers markedly inhibits cellularization and fragmentation, and lineage tracing demonstrates that cycling mononucleate cells arise from single Msx1-expressing fibers. Morpholino antisense knockdown in isolated myofibers, microinjection lineage tracing, time-lapse microscopy PLoS biology High 15314647
2004 In dorsal neural tube, Msx1 overexpression induces roof-plate cell fate and increased apoptosis while repressing neuronal differentiation, activities that are downstream of BMP signaling; Msx3 (but not Msx1) phenocopies later BMP-driven dorsal interneuron specification, indicating that the two paralogs mediate distinct temporal aspects of BMP signaling. Overexpression in chick neural tube, in situ hybridization, cell fate analysis Development Medium 14973289
2005 Pax9 physically associates with Msx1 in vivo and in vitro (co-IP and GST pulldown); their combined co-expression is required in the dental mesenchyme for maintaining Bmp4 expression, and genetic epistasis in double mutants shows synergistic regulation of molar tooth formation. Co-immunoprecipitation, GST interaction assay, compound mutant mouse analysis Archives of oral biology Medium 15721141
2003 Msx1 and Bmp4 operate in a genetic pathway regulating alveolar bone formation, with Dlx5 and Cbfa1 acting downstream of Msx1/Bmp4; Bmp4 ectopic expression restores Dlx5 (but not Cbfa1) in Msx1 null dental mesenchyme and rescues both in the developing alveolar bone. Msx1 knockout and Cbfa1 knockout mice, in situ hybridization, transgenic Bmp4 expression rescue Mechanisms of development High 14654219
2001 An endogenous Msx1 antisense RNA (Msx1-AS RNA) exists in mice, rats, and humans; it is expressed inversely to Msx1 protein in differentiated dental and bone cells, and the balance between Msx1 sense and antisense RNAs regulates Msx1 protein levels. Dlx5 abrogates Msx1-AS RNA expression, revealing crosstalk between Msx-Dlx pathways. Msx1 down-regulates Cbfa1, a master regulator of skeletal cell differentiation. In situ hybridization, overexpression in odontoblastic cell line (MO6-G3), primer extension for transcription initiation site PNAS Medium 11390985
2007 Msx1 and Msx2 in double-null mice fail to form the frontal bone due to a defect in differentiation of cranial neural crest (CNC)-derived frontal mesenchyme; mechanistically, Msx genes are required for expression of Runx2 in the frontonasal CNC subpopulation, controlling osteogenic lineage differentiation. Msx1/Msx2 double knockout mice, CNC lineage tracing, in situ hybridization for Runx2 Mechanisms of development High 17693062
2007 Msx1 expression in limb bud muscle precursor cells (co-expressing Pax3) is driven by a conserved 78 bp proximal enhancer sub-domain that is dependent on canonical Wnt/TCF4 signaling; in vivo ChIP confirms TCF4 binding to this element, mechanistically linking Wnt/TCF and Msx1/Pax3/MyoD pathways. Transgenic mouse analysis, in vivo ChIP, comparative genomics, in situ hybridization, immunohistochemistry, explant culture with Wnt pathway manipulation Developmental biology High 17727834
2008 MSX1 acts downstream of PHOX2B in neuroblastoma; MSX1 induction strongly upregulates DLK1, NOTCH3, and HEY1, activating the Delta-Notch pathway, and causes cleavage of NOTCH3 to its active form, linking MSX1 to Delta-Notch pathway regulation. Inducible overexpression, Affymetrix microarray, Northern blot, Western blot (NOTCH3 cleavage) Experimental cell research Medium 18201699
2011 Osr2 forms stable protein complexes with Msx1 (and weakly with Pax9) in co-transfected cells; Osr2 acts downstream of Pax9 and patterns the mesenchymal odontogenic field through protein-protein interactions with Msx1 and Pax9. Deletion of Osr2 rescues molar tooth morphogenesis in Msx1-/- mice. Co-immunoprecipitation, Osr2/Pax9/Msx1 compound mutant mice, genetic rescue analysis Developmental biology High 21420399
2013 Msx1 and Tbx2 are induced by epithelial Bmp4 in dental mesenchyme and physically interact; Tbx2 antagonizes Msx1 activity on the Bmp4 promoter, and partial loss of Tbx2 (Tbx2+/-) rescues the bud-stage tooth arrest in Msx1-/- mice by restoring enamel knot formation and mesenchymal Bmp4 expression. Co-immunoprecipitation in C3H10T1/2 cells, Tbx2/Msx1 compound mutant mice, Tbx2 knockdown (siRNA), in situ hybridization Development High 23720046
2014 Msx1 and Msx2 proteins directly activate Atoh1 transcription by binding homeodomain-recognition sites in the Atoh1 3' enhancer in vitro; in vivo ChIP confirms Msx1 binding to the Atoh1 enhancer, and Msx1/Msx2 double null mice lack Atoh1 expression and dI1 interneurons in the dorsal spinal cord. In vitro transcriptional activation assay, ChIP, Msx1/Msx2 double knockout mice, cell lineage analysis Development High 24715462
2013 A novel non-stop mutation in MSX1 (p.*304Tyrext*48) causes oligodontia; the mutant protein is expressed but fails to enter the nucleus, demonstrating that the C-terminus region is required for nuclear localization of MSX1. DNA sequencing, in vitro expression of mutant protein, subcellular localization by immunofluorescence in transfected cells Mutagenesis Medium 24914010
2013 Wild-type MSX1 localizes exclusively to the nuclear periphery; a truncated MSX1 lacking the homeodomain/MH4 (W139X mutant) is stable but localizes diffusely throughout the cell, demonstrating that the homeodomain/MH4 region contains sequences essential for nuclear peripheral targeting. Immunofluorescence subcellular localization of wild-type and mutant MSX1 in transfected cells European journal of oral sciences Medium 24329876
2014 MSX1 homeodomain mutations T174I and L205R abolish DNA binding ability (shown by EMSA) and eliminate suppression of MyoD promoter activity, but do not affect protein stability or nuclear localization. These mutations also impair interaction with EZH2 methyltransferase, suggesting that EZH2-Msx1 interaction mediates gene suppression. EMSA (electrophoretic mobility shift assay), co-immunoprecipitation with EZH2, reporter assay (MyoD promoter), nuclear localization by immunofluorescence PLoS one High 25101640
2014 In vascular myofibroblasts, Msx1 selectively maintains Shh expression while Msx2 sustains Wnt2, Wnt5a, and Sca1 expression; together Msx1+Msx2 support TNAP and Wnt7b expression and drive osteogenic programming in diabetic arteriosclerosis. Targeted deletion of vascular Msx1+Msx2 reduces arterial calcification and aortic stiffness. Smooth muscle cell-specific conditional Msx1/Msx2 double knockout (SM22-Cre), RNA interference in myofibroblast cultures, pulse wave velocity measurement, gene expression analysis Diabetes Medium 25056439
2016 In human dental pulp stem cells, MSX1 knockdown abolishes osteogenic differentiation (RUNX2, BMP2, alkaline phosphatase, osteocalcin induction, and calcification) and simultaneously induces SREBP2 and cholesterol synthesis genes, suggesting MSX1 promotes osteoblast differentiation partly by downregulating cholesterol biosynthesis genes. siRNA knockdown, DNA microarray, qPCR, alkaline phosphatase activity assay, mineralization assay in primary human cells Stem cells international Medium 27648077
2016 Msx1 and Osr2 antagonistically regulate secreted Wnt antagonists (Dkk2, Sfrp2) in the tooth bud mesenchyme; Msx1 loss increases Dkk2 and Sfrp2 expression, and pharmacological Wnt pathway activation (LiCl, DKK inhibition) or genetic inactivation of Sfrp2/3 combined with DKK inhibition rescues molar tooth morphogenesis in Msx1-/- mice. RNA-seq of tooth mesenchyme, compound mutant mice, pharmacological Wnt pathway activation in utero Developmental biology High 27713059
2020 CDK1-mediated phosphorylation of Msx1 at Ser136 is critical for Msx1 to upregulate Fgf9 and Fgf18 expression; Msx1 directly binds to Fgf9 and Fgf18 promoters, and the resulting FGF9/18 signals activate ERK1/2 (MAPK) to promote myoblast and mesenchymal stem cell proliferation during limb development. Phosphorylation site mutagenesis, ChIP (Msx1 binding to Fgf9/18 promoters), antibody neutralization of FGF9/18, mesenchymal-specific Msx1/2 conditional knockout mice, Western blot for pERK1/2 Nucleic acids research High 33080014

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1994 Msx1 deficient mice exhibit cleft palate and abnormalities of craniofacial and tooth development. Nature genetics 1046 7914451
1996 A human MSX1 homeodomain missense mutation causes selective tooth agenesis. Nature genetics 542 8696335
1997 Xenopus msx1 mediates epidermal induction and neural inhibition by BMP4. Development (Cambridge, England) 277 9272945
2005 Msx1 and Pax3 cooperate to mediate FGF8 and WNT signals during Xenopus neural crest induction. Developmental cell 266 15691759
1998 Association of MSX1 and TGFB3 with nonsyndromic clefting in humans. American journal of human genetics 242 9683588
1992 Expression of Hox-7.1 in myoblasts inhibits terminal differentiation and induces cell transformation. Nature 200 1360150
2004 MSX1 cooperates with histone H1b for inhibition of transcription and myogenesis. Science (New York, N.Y.) 195 15192231
1995 Digit tip regeneration correlates with regions of Msx1 (Hox 7) expression in fetal and newborn mice. Development (Cambridge, England) 193 7538067
2003 Digit regeneration is regulated by Msx1 and BMP4 in fetal mice. Development (Cambridge, England) 179 12944425
2001 A nonsense mutation in MSX1 causes Witkop syndrome. American journal of human genetics 172 11369996
2005 Combined deficiencies of Msx1 and Msx2 cause impaired patterning and survival of the cranial neural crest. Development (Cambridge, England) 154 16221730
1993 Expression of homeobox genes Msx-1 (Hox-7) and Msx-2 (Hox-8) during cardiac development in the chick. Developmental dynamics : an official publication of the American Association of Anatomists 143 8106021
1991 Hox-7 expression during murine craniofacial development. Development (Cambridge, England) 136 1685989
1991 Chicken homeobox gene Msx-1: structure, expression in limb buds and effect of retinoic acid. Development (Cambridge, England) 133 1685987
1995 MSX1 inhibits myoD expression in fibroblast x 10T1/2 cell hybrids. Cell 126 7664340
2011 Isolated oligodontia associated with mutations in EDARADD, AXIN2, MSX1, and PAX9 genes. American journal of medical genetics. Part A 117 21626677
1996 Comparison of MSX-1 and MSX-2 suggests a molecular basis for functional redundancy. Mechanisms of development 117 8861098
2010 Genetic interactions between Pax9 and Msx1 regulate lip development and several stages of tooth morphogenesis. Developmental biology 114 20123092
2005 Analysis of Msx1; Msx2 double mutants reveals multiple roles for Msx genes in limb development. Development (Cambridge, England) 113 15930102
2007 Concerted action of Msx1 and Msx2 in regulating cranial neural crest cell differentiation during frontal bone development. Mechanisms of development 110 17693062
2000 BMP4 rescues a non-cell-autonomous function of Msx1 in tooth development. Development (Cambridge, England) 108 11023873
2006 Functional consequences of interactions between Pax9 and Msx1 genes in normal and abnormal tooth development. The Journal of biological chemistry 101 16651263
2004 Distinct activities of Msx1 and Msx3 in dorsal neural tube development. Development (Cambridge, England) 97 14973289
2001 Endogenous Msx1 antisense transcript: in vivo and in vitro evidences, structure, and potential involvement in skeleton development in mammals. Proceedings of the National Academy of Sciences of the United States of America 96 11390985
1995 Differential expression of myogenic regulatory genes and Msx-1 during dedifferentiation and redifferentiation of regenerating amphibian limbs. Developmental dynamics : an official publication of the American Association of Anatomists 95 7703517
1999 The homeobox gene Msx1 is expressed in a subset of somites, and in muscle progenitor cells migrating into the forelimb. Development (Cambridge, England) 93 10331980
1995 Ectoderm-mesenchyme and mesenchyme-mesenchyme interactions regulate Msx-1 expression and cellular differentiation in the murine limb bud. Developmental biology 91 7537232
2006 PIAS1 confers DNA-binding specificity on the Msx1 homeoprotein. Genes & development 82 16600910
1995 Gene defect in hypodontia: exclusion of MSX1 and MSX2 as candidate genes. Human genetics 81 7649547
1990 The human homeobox gene HOX7 maps to chromosome 4p16.1 and may be implicated in Wolf-Hirschhorn syndrome. Human genetics 78 1969845
2007 Msx1 and Msx2 regulate survival of secondary heart field precursors and post-migratory proliferation of cardiac neural crest in the outflow tract. Developmental biology 77 17601530
2004 A balance between the anti-apoptotic activity of Slug and the apoptotic activity of msx1 is required for the proper development of the neural crest. Developmental biology 76 15501222
2004 A novel MSX1 mutation in hypodontia. American journal of medical genetics. Part A 75 15264286
2004 The regenerative plasticity of isolated urodele myofibers and its dependence on MSX1. PLoS biology 74 15314647
2008 Msx1 and Msx2 are required for endothelial-mesenchymal transformation of the atrioventricular cushions and patterning of the atrioventricular myocardium. BMC developmental biology 70 18667074
2014 Targeted reduction of vascular Msx1 and Msx2 mitigates arteriosclerotic calcification and aortic stiffness in LDLR-deficient mice fed diabetogenic diets. Diabetes 66 25056439
2008 The MSX1 homeobox transcription factor is a downstream target of PHOX2B and activates the Delta-Notch pathway in neuroblastoma. Experimental cell research 65 18201699
1991 Structure and sequence of the human homeobox gene HOX7. Genomics 65 1685479
2006 MSX1 and orofacial clefting with and without tooth agenesis. Journal of dental research 63 16723652
1993 Experimental analysis of the control of expression of the homeobox-gene Msx-1 in the developing limb and face. Development (Cambridge, England) 62 7903926
1992 Multiple sites of Hox-7 expression during mouse embryogenesis: comparison with retinoic acid receptor mRNA localization. Molecular reproduction and development 57 1353971
2006 A novel missense mutation in MSX1 underlies autosomal recessive oligodontia with associated dental anomalies in Pakistani families. Journal of human genetics 52 16932841
1996 Regulated expression of homeobox genes Msx-1 and Msx-2 in mouse mammary gland development suggests a role in hormone action and epithelial-stromal interactions. Developmental biology 52 8660900
2000 The expression of the homeobox gene Msx1 reveals two populations of dermal progenitor cells originating from the somites. Development (Cambridge, England) 48 10769239
2005 Studies on Pax9-Msx1 protein interactions. Archives of oral biology 47 15721141
2003 Cranial neural crest-derived mesenchymal proliferation is regulated by Msx1-mediated p19(INK4d) expression during odontogenesis. Developmental biology 47 12941628
2000 Absence of mutations in the homeodomain of the MSX1 gene in patients with hypodontia. American journal of medical genetics 47 10861665
2010 MTHFR and MSX1 contribute to the risk of nonsyndromic cleft lip/palate. European journal of oral sciences 46 20572854
2004 Msx-1 and Msx-2 in mammary gland development. Journal of mammary gland biology and neoplasia 45 15300013
2005 Expression and regulation of the Msx1 natural antisense transcript during development. Nucleic acids research 44 16157866
2016 Epigenetic Regulation of the Homeobox Gene MSX1 Associates with Platinum-Resistant Disease in High-Grade Serous Epithelial Ovarian Cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 42 26763252
2016 Bmp4-Msx1 signaling and Osr2 control tooth organogenesis through antagonistic regulation of secreted Wnt antagonists. Developmental biology 42 27713059
1997 Two enhancer domains control early aspects of the complex expression pattern of Msx1. Mechanisms of development 42 9106164
2010 PAX9 and MSX1 transcription factor genes in non-syndromic dental agenesis. Archives of oral biology 41 21111400
2008 Identification of a novel missense mutation of MSX1 gene in Chinese family with autosomal-dominant oligodontia. Archives of oral biology 41 18374898
2003 Msx1/Bmp4 genetic pathway regulates mammalian alveolar bone formation via induction of Dlx5 and Cbfa1. Mechanisms of development 41 14654219
1995 Expression and activity of the newt Msx-1 gene in relation to limb regeneration. Proceedings. Biological sciences 41 7732036
2011 Msx1 and Msx2 in limb mesenchyme modulate digit number and identity. Developmental dynamics : an official publication of the American Association of Anatomists 39 21465616
2012 Novel MSX1 mutation in a family with autosomal-dominant hypodontia of second premolars and third molars. Archives of oral biology 37 22297032
2011 Osr2 acts downstream of Pax9 and interacts with both Msx1 and Pax9 to pattern the tooth developmental field. Developmental biology 37 21420399
2000 The Dlx3 protein harbors basic residues required for nuclear localization, transcriptional activity and binding to Msx1. Journal of cell science 37 11058088
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2000 Craniofacial disorders caused by mutations in homeobox genes MSX1 and MSX2. Journal of craniofacial genetics and developmental biology 36 10879654
2006 Tissue response and Msx1 expression after human fetal digit tip amputation in vitro. Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society 35 16939566
1998 Association between homeobox-containing gene MSX1 and the occurrence of limb deficiency. American journal of medical genetics 34 9482651
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2005 Ventral abdominal wall dysmorphogenesis of Msx1/Msx2 double-mutant mice. The anatomical record. Part A, Discoveries in molecular, cellular, and evolutionary biology 33 15803476
2004 Msx1 disruption leads to diencephalon defects and hydrocephalus. Developmental dynamics : an official publication of the American Association of Anatomists 33 15188430
2011 Sequence analysis of PAX9, MSX1 and AXIN2 genes in a Chinese oligodontia family. Archives of oral biology 32 21530942
2007 A highly conserved Wnt-dependent TCF4 binding site within the proximal enhancer of the anti-myogenic Msx1 gene supports expression within Pax3-expressing limb bud muscle precursor cells. Developmental biology 32 17727834
2014 Repressed BMP signaling reactivates NKL homeobox gene MSX1 in a T-ALL subset. Leukemia & lymphoma 31 24844359
2014 A novel non-stop mutation in MSX1 causing autosomal dominant non-syndromic oligodontia. Mutagenesis 31 24914010
2001 Postnatal Msx1 expression pattern in craniofacial, axial, and appendicular skeleton of transgenic mice from the first week until the second year. Developmental dynamics : an official publication of the American Association of Anatomists 31 11357189
2009 HYD1-induced increase in reactive oxygen species leads to autophagy and necrotic cell death in multiple myeloma cells. Molecular cancer therapeutics 30 19671765
2013 Msx1 and Tbx2 antagonistically regulate Bmp4 expression during the bud-to-cap stage transition in tooth development. Development (Cambridge, England) 29 23720046
2004 Msx1-deficient mice fail to form prosomere 1 derivatives, subcommissural organ, and posterior commissure and develop hydrocephalus. Journal of neuropathology and experimental neurology 29 15217086
2018 MSX1 induces G0/G1 arrest and apoptosis by suppressing Notch signaling and is frequently methylated in cervical cancer. OncoTargets and therapy 28 30127625
2013 Msx1 regulates proliferation and differentiation of mouse dental mesenchymal cells in culture. European journal of oral sciences 28 24028588
2013 BMP-mediated functional cooperation between Dlx5;Dlx6 and Msx1;Msx2 during mammalian limb development. PloS one 25 23382810
2013 Novel nonsense mutation in MSX1 in familial nonsyndromic oligodontia: subcellular localization and role of homeodomain/MH4. European journal of oral sciences 25 24329876
2011 Idiopathic and heritable PAH perturb common molecular pathways, correlated with increased MSX1 expression. Pulmonary circulation 25 22140629
2004 Cloning and characterization of a gene coding for a hydrophobin, Fv-hyd1, specifically expressed during fruiting body development in the basidiomycete Flammulina velutipes. Applied microbiology and biotechnology 25 15834718
2016 Msx1 and Msx2 function together in the regulation of primordial germ cell migration in the mouse. Developmental biology 24 27435625
2011 Acquisition of resistance toward HYD1 correlates with a reduction in cleaved α4 integrin expression and a compromised CAM-DR phenotype. Molecular cancer therapeutics 24 21980133
2001 Msx3 protein recruits histone deacetylase to down-regulate the Msx1 promoter. The Biochemical journal 24 11115394
2019 Elicitor hydrophobin Hyd1 interacts with Ubiquilin1-like to induce maize systemic resistance. Journal of integrative plant biology 23 30803127
2014 Msx1 and Msx2 act as essential activators of Atoh1 expression in the murine spinal cord. Development (Cambridge, England) 23 24715462
2014 Characterization of novel MSX1 mutations identified in Japanese patients with nonsyndromic tooth agenesis. PloS one 23 25101640
2012 Wnt/β-catenin signaling and Msx1 promote outgrowth of the maxillary prominences. Frontiers in physiology 23 23055979
2007 Conditional alleles of Msx1 and Msx2. Genesis (New York, N.Y. : 2000) 23 17654563
2006 Msx1 and Msx2 have shared essential functions in neural crest but may be dispensable in epidermis and axis formation in Xenopus. The International journal of developmental biology 23 16586351
2020 Msx1 deficiency interacts with hypoxia and induces a morphogenetic regulation during mouse lip development. Development (Cambridge, England) 22 32467233
2003 Selection on coding regions determined Hox7 genes evolution. Molecular biology and evolution 22 12949154
2022 LINC01021 maintains tumorigenicity by enhancing N6-methyladenosine reader IMP2 dependent stabilization of MSX1 and JARID2: implication in colorectal cancer. Oncogene 21 35173309
2020 Hedgehog signaling controls segmentation dynamics and diversity via msx1 in a spider embryo. Science advances 21 32917677
2017 Msh homeobox 1 (Msx1)- and Msx2-overexpressing bone marrow-derived mesenchymal stem cells resemble blastema cells and enhance regeneration in mice. The Journal of biological chemistry 20 28461333
2013 MTI-101 (cyclized HYD1) binds a CD44 containing complex and induces necrotic cell death in multiple myeloma. Molecular cancer therapeutics 20 24048737
2014 Oncogenic deregulation of NKL homeobox gene MSX1 in mantle cell lymphoma. Leukemia & lymphoma 19 24237447
2020 Phosphorylation of Msx1 promotes cell proliferation through the Fgf9/18-MAPK signaling pathway during embryonic limb development. Nucleic acids research 18 33080014
2016 Reduced homeobox protein MSX1 in human endometrial tissue is linked to infertility. Human reproduction (Oxford, England) 18 27312535