| 2003 |
Sp8 functions downstream of Wnt3, Fgf10, and Bmpr1a in the signaling cascade that mediates AER formation; targeted deletion of Sp8 prevents progression to a mature AER despite initial induction of AER precursor cells and appropriate marker gene expression. |
Targeted gene deletion (knockout mouse), in situ hybridization, genetic epistasis analysis |
Proceedings of the National Academy of Sciences of the United States of America |
High |
14526104
|
| 2004 |
Sp8 and Sp9 are ectodermal targets of Fgf10 mesenchymal signaling and act as positive transcriptional regulators of Fgf8 expression in the AER to control limb outgrowth; Wnt/β-catenin signaling positively regulates Sp8 but not Sp9. |
Overexpression in chick embryos, dominant-negative constructs in chick, morpholino knockdown in zebrafish, embryological and genetic analyses |
Development (Cambridge, England) |
High |
15358670
|
| 2006 |
Sp8 is required for normal generation of calretinin-expressing and GABAergic/nondopaminergic olfactory bulb interneuron subtypes; conditional inactivation in the embryonic ventral telencephalon increases cell death in the lateral ganglionic eminence and rostral migratory stream and causes misspecification and abnormal migration of neuroblasts/interneurons. |
Conditional knockout (Cre-lox), immunostaining, cell death assays |
Neuron |
High |
16476661
|
| 2006 |
Loss of Sp8 causes a posterior shift of the isthmic organizer (IsO) and ectopic expression of Fgf8, Otx2, and Wnt1 in the rostral hindbrain; Sp8 restricts Fgf8 expression at the IsO and controls cell proliferation in the mid- and hindbrain. |
Knockout mouse analysis, in situ hybridization, immunostaining |
Development (Cambridge, England) |
Medium |
16571633
|
| 2007 |
Sp8 binds Fgf8 regulatory elements and acts as a direct transcriptional activator of Fgf8 in vitro; Fgf8 and Sp8 exhibit reciprocal induction in the embryonic telencephalon; Emx2 represses Sp8 induction of Fgf8 in vitro, limiting Fgf8 expression to the commissural plate. |
In vitro transcription assays, in utero electroporation of full-length and chimeric (dominant-negative) expression constructs, gain- and loss-of-function studies |
Neural development |
High |
17509151
|
| 2007 |
Sp8 conditional inactivation disrupts anteroposterior patterning of the telencephalon by modulating Emx2 and Pax6 expression gradients; Sp8 maintains ventral cell identity in the septum and MGE through positive regulatory interaction with Fgf8 and Nkx2.1, independent of SHH and WNT signaling; Sp8 is required to sustain cortical progenitor pools, control preplate splitting, and specify cellular diversity within cortical layers. |
Conditional inactivation (Cre-lox), in situ hybridization, immunostaining |
Neural development |
High |
17470284
|
| 2013 |
Sp8 misexpression throughout the telencephalon represses COUP-TF1 expression (a negative effector of Fgf signaling), while COUP-TF1 misexpression downregulates Sp8, establishing reciprocal cross-regulation; Sp8 misexpression increases Fgf target gene expression, indicating enhanced Fgf signaling in pallial progenitors. |
Binary transgenic misexpression system in mice, conditional ablation, immunostaining, in situ hybridization |
Cerebral cortex (New York, N.Y. : 1991) |
Medium |
23307639
|
| 2013 |
Sp8 is required in the anterior neural ridge (ANR) and olfactory pit (OP) signaling centers to maintain Fgf8 and Fgf17 expression; partial rescue of Sp8 mutant craniofacial phenotype achieved by reducing SHH signaling, placing Sp8 upstream of SHH-dependent patterning. |
Conditional knockout, laser capture microdissection with microarrays, in situ hybridization, immunostaining, genetic and pharmaceutical rescue |
Developmental biology |
High |
23872235
|
| 2014 |
Sp8 and Sp6 act together in a dose-dependent manner as indispensable mediators of Wnt/β-catenin and Bmp signaling in the limb ectoderm; combined elimination of Sp6 and Sp8 prevents activation of both Fgf8 and En1, leading to tetra-amelia. |
Double conditional knockout mice (Sp6-/-;Sp8 conditional), genetic epistasis, in situ hybridization |
PLoS genetics |
High |
25166858
|
| 2014 |
Sp8 plays a supplementary role to Pax6 in establishing the pMN/p3 domain boundary in the spinal cord through mutually repressive interactions with Nkx2-2; Sp8 functions as a transcriptional activator, and a repressive form of Sp8 selectively inhibits motor neuron generation and induces ectopic Nkx2-2 expression. |
Conditional knockout, in utero electroporation of dominant-negative and activating Sp8 constructs, immunostaining, in situ hybridization |
Development (Cambridge, England) |
High |
24948600
|
| 2014 |
In Xenopus, loss of sp8 results in otic dysmorphogenesis (enlarged, uncompartmentalized otic vesicles, abnormal sensory organs); overexpression of sp8 is sufficient to induce ectopic otic vesicles with sensory hair cells, neurofilament innervation, and otoconia. |
Forward genetic screen, TALEN loss-of-function, morpholino knockdown, overexpression in Xenopus tropicalis |
Proceedings of the National Academy of Sciences of the United States of America |
High |
24722637
|
| 2016 |
Sp8 (together with Sp5) binds directly to GC boxes in Wnt target gene enhancers and physically interacts with chromatin-bound Tcf1/Lef1 to facilitate recruitment of β-catenin to Wnt target gene enhancers, acting as a gene-specific transcriptional coactivator in the Wnt/β-catenin pathway. |
ChIP in mouse embryos and differentiating ES cells, co-immunoprecipitation, reporter assays, conditional genetics |
Proceedings of the National Academy of Sciences of the United States of America |
High |
26969725
|
| 2018 |
SP8 and SP9 coordinately drive expression of Six3 in a spatially restricted LGE subventricular zone domain to promote D2 MSN generation; ChIP-Seq shows SP9 directly binds the Six3 promoter and a putative enhancer, and conditional deletion of Six3 phenocopies Sp8/9 double mutants. |
Conditional deletion, RNA-Seq, ChIP-Seq, in situ hybridization |
Development (Cambridge, England) |
High |
29967281
|
| 2018 |
SP8 and SP9 coordinately regulate olfactory bulb interneuron development; double conditional deletion causes severe reduction of OB interneuron number via defects in neuronal differentiation, tangential and radial migration, and increased cell death; Sp8/Sp9 double mutant neuroblasts fail to express Prokr2 and Tshz1. |
Conditional double knockout (Cre-lox), RNA-Seq, RNA in situ hybridization, immunostaining |
Cerebral cortex (New York, N.Y. : 1991) |
High |
28981617
|
| 2018 |
SP8 binds the Cyclin D1 (Ccnd1) locus at exon regions (genome-wide ChIP) and shows binding activity at the Ccnd1 gene 3'-end in vitro; alteration of Sp8 expression in vivo affects Ccnd1 expression during early corticogenesis, suggesting SP8 modulates PAX6-mediated repression of Ccnd1. |
Genome-wide ChIP assay, in vitro binding assay, mouse genetics (Sp8 gain/loss-of-function) |
Frontiers in neuroscience |
Medium |
29599703
|
| 2019 |
Sp8/Sp9 coordinately regulate CGE-derived cortical interneuron development; conditional double knockout causes loss of CGE-derived cortical interneurons with migration defects (longer leading processes, ectopic accumulation); Sp8/9 repress Pak3, Robo1, and Slit1 expression; Cxcl14 expression in CGE-derived interneurons is critically dependent on SP8. |
Conditional double knockout (Gsx2-Cre and Dlx5/6-CIE), immunostaining, in situ hybridization |
The Journal of comparative neurology |
Medium |
31070778
|
| 2019 |
SP8 and SP9 coordinately regulate MGE-derived PV+ cortical interneuron tangential migration; Sp8/Sp9 double conditional KO causes severe loss of PV+ cortical interneurons due to migration defects, at least in part through regulating EphA3, Ppp2r2c, and Rasgef1b expression. |
Conditional double knockout, immunostaining, in situ hybridization |
Frontiers in molecular neuroscience |
Medium |
31001083
|
| 2020 |
SP8 directly binds the FGF8 promoter (chromatin immunoprecipitation) and transcriptionally activates FGF8 expression in hepatoblastoma; SP8 gain-of-function promotes cell motility, self-renewal, migration, invasion, and EMT; CRISPR-dCas9 interference against FGF8 abolishes SP8-mediated aggressive tumor behavior, placing FGF8 downstream of SP8. |
Chromatin immunoprecipitation, gain- and loss-of-function experiments, KRAB-dCas9 interference, clonogenicity assays, migration/invasion assays |
Cancers |
High |
32824198
|
| 2021 |
Sp8 misexpression in the ventral telencephalic SVZ increases generation of amygdala intercalated cells (ITCs) in a Tshz1 gene dosage-dependent manner and impairs rostral migration of OB interneurons; Sp8 has temporally distinct roles in LGE neurogenesis, with early expression critical for striatal, amygdala, and OB interneuron generation. |
Genetic gain-of-function misexpression in mice (binary transgenic), conditional genetics, immunostaining, in situ hybridization |
Cerebral cortex (New York, N.Y. : 1991) |
Medium |
33230547
|
| 2025 |
SP5 and SP8 regulate primary and motile cilia formation in mouse embryos; loss of both Sp5 and Sp8 results in shorter and fewer cilia across cell types causing situs inversus and hydrocephalus; expression of SP8 alone is sufficient to induce primary cilia in unciliated cells. |
Conditional genetics in mouse embryos, stem cell experiments, multiomics (transcriptomics), gain-of-function (SP8 expression in unciliated cells) |
Science (New York, N.Y.) |
High |
40875857
|
| 2025 |
SP5 and SP8 maintain neuromesodermal competent progenitor (NMC) identity by cooperating with Tbxt, Tcf7, and Cdx2 to sustain an autoregulatory Wnt/Fgf network; SP5/8 bind a novel enhancer essential for Wnt3a expression; mechanistically, SP5/8 regulate the dynamic exchange of activating and repressive Tcf complexes at Wnt-responsive enhancers. |
Conditional genetics, ChIP/chromatin analysis, multiomics (Sp5/8 binding at enhancers), reporter assays |
bioRxivpreprint |
Medium |
bio_10.1101_2025.06.03.657492
|