| 2008 |
Shroom3 directly binds ROCK1/2 and recruits them to epithelial apical junctions; a Shroom3-binding site (RII-C1) on ROCKs was identified, and dominant-negative RII-C1 disrupts Shroom3-ROCK interaction, removing apically localized ROCKs and blocking neural tube closure. |
Co-immunoprecipitation, dominant-negative domain expression, immunofluorescence localization, Xenopus neural tube closure assay |
Development |
High |
18339671
|
| 2010 |
Shroom3 is required for apical localization of F-actin, myosin II, and Vasp during lens placode invagination, and Shroom3 expression in the lens is transcriptionally activated by Pax6. |
Loss-of-function mouse genetics, immunofluorescence for F-actin/myosin II/Vasp, genetic epistasis with Pax6 mutants |
Development |
High |
20081189
|
| 2010 |
Pitx transcription factors directly activate Shroom3 transcription via Pitx-responsive regulatory elements in the Shroom3 genomic locus, and ectopic Pitx expression is sufficient to induce Shroom3-dependent cytoskeletal reorganization and epithelial cell shape change in Xenopus gut. |
Reporter assays with Pitx-responsive elements, gain-of-function Pitx expression, loss-of-function Shroom3 morpholino knockdown, immunofluorescence |
Development |
High |
20332151
|
| 2011 |
A Trio (RhoA-GEF)–RhoA–Shroom3 pathway is required for apical constriction during lens pit invagination; RhoA activity is required for Shroom3 apical localization, and apically targeted active RhoA is sufficient to induce apical constriction. |
Dominant-negative/constitutively active RhoA constructs, Trio knockdown in MDCK cells and mouse lens pit, Rock inhibitor, immunofluorescence |
Development |
High |
22031541
|
| 2011 |
Shroom3 functions cooperatively with N-cadherin downstream of Pitx2 to regulate asymmetric epithelial cell shape changes in the dorsal mesentery required for gut rotation; genetic interaction shown by compound heterozygotes. |
Mouse genetics, compound heterozygous analysis, cell morphology measurements |
Developmental biology |
Medium |
21726547
|
| 2012 |
Shroom3 expression downstream of FGF signaling organizes cell shape changes during rosette assembly in the zebrafish lateral line primordium by recruiting Rho kinase and activating non-muscle myosin. |
Gain- and loss-of-function experiments in zebrafish, immunofluorescence for myosin, FGF pathway inhibition, rosette quantification |
Development |
High |
23136387
|
| 2014 |
An ENU-induced R1838C substitution in mouse Shroom3 abolishes ROCK binding without affecting Shroom3 expression or localization, rendering it non-functional for cell morphology regulation and causing neural tube defects, demonstrating ROCK is the major downstream effector of Shroom3 in neural tube morphogenesis. |
ENU mutagenesis, biochemical binding assays, in vivo neural tube closure phenotyping, sequence conservation analysis |
Biology open |
High |
25171888
|
| 2014 |
p120-catenin is required for apical constriction of lens cells and functions by recruiting Shroom3 to adherens junctions; genetic interaction and junctional mislocalization of Shroom3 demonstrated in p120-catenin mutants. |
Mouse genetic interaction (compound heterozygotes), immunofluorescence localization of Shroom3 and p120-catenin, apical constriction quantification |
Development |
Medium |
25038041
|
| 2014 |
Shroom3 facilitates canonical TGF-β1 signaling and increases COL1A1 expression in renal tubular cells; this is regulated by a TCF7L2-dependent enhancer at the rs17319721 locus that increases SHROOM3 transcription in response to TGF-β1/β-catenin signaling; tubular-specific knockdown of Shroom3 abrogates interstitial fibrosis in UUO mice. |
Luciferase reporter assay for enhancer function, siRNA knockdown in tubular cells, inducible tubular-specific mouse knockdown, UUO fibrosis model, qRT-PCR, Western blot |
Journal of Clinical Investigation |
High |
25437874
|
| 2014 |
Variants disrupting the actin-binding domain of SHROOM3 impair podocyte function and the glomerular filtration barrier; wild-type SHROOM3 but not FHH rat SHROOM3 allele rescues glomerular defects in zebrafish shroom3 knockdown. |
Congenic rat mapping, zebrafish rescue experiments with wild-type vs. mutant alleles, functional complementation |
Genome research |
Medium |
25273069
|
| 2015 |
Shroom3 functions downstream of planar cell polarity (PCP) signaling during neural tube closure; Shroom3 and Dishevelled 2 co-distribute and form a physical complex; components of the Shroom3 pathway are planar-polarized along mediolateral junctions in a Shroom3- and PCP-dependent manner. |
Co-immunoprecipitation of Shroom3 and Dishevelled 2, genetic epistasis (Shroom3/Vangl2 and Shroom3/Wnt5a double mutants), immunofluorescence of polarized distribution |
Biology open |
High |
25596276
|
| 2015 |
A small molecule (CCG-17444) covalently targets Shroom3 Cys1816 to inhibit the Shroom3–Rho kinase protein-protein interaction in vitro and counteracts Nogo66-mediated inhibition of neurite outgrowth, demonstrating that Shroom3-ROCK interaction transduces Nogo66 inhibitory signals. |
High-throughput screen, in vitro protein-protein interaction assay, covalent mechanism characterization, neurite outgrowth assay with Nogo66 |
BMC neuroscience |
Medium |
26077244
|
| 2016 |
CDC42 is required upstream of SHROOM3 for apical constriction during thyroid bud morphogenesis; SHROOM3 is expressed in the thyroid bud and its subcellular localization is disrupted in Cdc42-deficient embryos; Shroom3 gene trap mutants fail to exhibit apical constriction in the thyroid bud epithelium. |
Conditional Cdc42 knockout, Shroom3 gene trap mutants, immunofluorescence localization, morphological analysis of thyroid bud |
Biology open |
Medium |
26772200
|
| 2016 |
Shroom3 null mice exhibit glomerular abnormalities including cystic and collapsing glomeruli and disrupted podocyte arrangement; these defects are associated with altered Rho-kinase/myosin II signaling and loss of apically distributed actin in podocytes. |
Shroom3 null mouse analysis, immunofluorescence for myosin II and F-actin, renal histology, electron microscopy |
Journal of the American Society of Nephrology |
High |
26940091
|
| 2018 |
SHROOM3 interacts with FYN (a Src kinase) via a critical SH3-binding domain distinct from its ROCK-binding domain; Shroom3-Fyn interaction is required for activation of Fyn kinase and downstream nephrin phosphorylation in podocytes; Shroom3 knockdown induces albuminuria with podocyte foot process effacement. |
Co-immunoprecipitation of endogenous SHROOM3 with FYN in human podocytes, domain mapping, inducible shRNA knockdown mouse model, electron microscopy, glomerular RNA-sequencing |
Journal of the American Society of Nephrology |
High |
30341149
|
| 2018 |
A CKD-associated SHROOM3 variant (P1244L) attenuates the interaction of SHROOM3 with 14-3-3 proteins, suggesting alterations to Hippo pathway signaling; additionally, the rs17319721 variant disrupts TCF7L2 binding to the SHROOM3 locus in podocyte nuclear extracts. |
Biophysical interaction assays, CRISPR/Cas9 editing, nuclear extract binding assays, cell transcription assays |
Journal of the American Society of Nephrology |
Medium |
29476007
|
| 2020 |
SHROOM3 interacts physically and genetically with Dishevelled 2 during cardiac development and is downstream of PCP signaling; loss of Shroom3 disrupts actomyosin cytoskeleton, cardiomyocyte polarity, and organization, causing congenital heart defects including ventricular septal defects and double outlet right ventricle. |
Co-immunoprecipitation of Shroom3 and Dishevelled 2, Shroom3 gene trap knockout mice, cardiac immunofluorescence for actomyosin components, genetic epistasis |
Developmental biology |
High |
32511952
|
| 2021 |
Shroom3 is required for epithelial repair and redifferentiation after ischemic AKI through organization of actomyosin regulators; Shroom3 heterozygous mice show disrupted Rho-kinase/myosin signaling and disorganized apical F-actin after tubular injury. |
Shroom3 heterozygous mouse ischemia-reperfusion model, immunofluorescence for actomyosin regulators, MDCK cell actin organization assay |
Kidney360 |
Medium |
35368578
|
| 2023 |
SHROOM3 knockout in brain organoids causes expansion of the apical lumen and reduced F-actin polarization, demonstrating that Shroom3 is required for apical constriction of neuroepithelial cells, sharing a pathogenic mechanism with valproic acid-induced NTDs. |
CRISPR/Cas9 knockout in human brain organoids, high-throughput image analysis, F-actin immunofluorescence, RNA sequencing |
Cells |
Medium |
37443734
|
| 2024 |
NRP1 interacts with Shroom3 via protein-protein interaction (confirmed by co-immunoprecipitation and protein docking); GAG-modified NRP1 recruits Shroom3, and non-GAG-modified NRP1 (S612A mutant) fails to recruit Shroom3 and cannot promote osteo/odontogenic differentiation in dental pulp stem cells. |
Co-immunoprecipitation, confocal colocalization, protein-protein docking, NRP1 S612A loss-of-function, Shroom3 knockdown |
Biochimica et Biophysica Acta - Molecular Cell Research |
Medium |
39033931
|
| 2024 |
Loss of SHROOM3 in cynomolgus monkey neuroepithelial organoids results in shorter neuroepithelial cells due to insufficient apical recruitment of F-actin, myosin II, and phospho-myosin light chain; these defects are not rescued by folate supplementation. |
SHROOM3 knockout in primate neuroepithelial organoids, immunofluorescence for cytoskeletal proteins, folate rescue experiments, RNA sequencing |
Zoological research |
Medium |
38287904
|
| 2025 |
The Shroom3 ASD2 domain (ROCK-binding domain) mediates profibrotic signaling in renal tubular cells and fibroblasts; ASD2-deletion mutant Shroom3 fails to activate ROCK (phospho-MYPT1), and transgenic mice overexpressing ASD2Δ-Sh3 show reduced TIF compared to WT-Sh3 mice; a distinct Fyn-binding motif in Shroom3 mediates its anti-proteinuric function. |
Transgenic mice overexpressing WT vs. ASD2Δ-Sh3, HEK293T/mIMCD cell lines, UUO and aristolochic nephropathy models, phospho-MYPT1 assay, Fyn-binding mutant mice, small molecule P2I inhibitors |
Nature communications |
High |
41469391
|
| 2025 |
VANGL2 and SHROOM3 cooperate in the splanchnic mesoderm to control bilateral symmetry during heart tube morphogenesis; apically localized VANGL2 acts through its downstream actin-binding effector SHROOM3. |
3D quantification of heart geometry in VANGL2 mutants, chick cell labeling, immunolocalization of VANGL2 and SHROOM3 |
bioRxiv (preprint)preprint |
Low |
bio_10.1101_2025.09.05.674213
|
| 2025 |
Shroom3 is required for optic fissure closure; it is apically localized in neural retina and RPE and its deficiency increases apical cell surface area, disrupts tissue alignment, and impairs reestablishment of apical-basal polarity during epithelial fusion. Neural retina-specific ablation shows RPE Shroom3 function is likely sufficient for tissue alignment. |
Shroom3 gene trap and floxed conditional knockout mice, immunofluorescence, neural retina-specific Cre ablation, morphological analysis |
Developmental biology |
Medium |
40113025
|