Unknown

Dataset Information

0

GAS1 is required for NOTCH-dependent facilitation of SHH signaling in the ventral forebrain neuroepithelium.


ABSTRACT: Growth arrest-specific 1 (GAS1) acts as a co-receptor to patched 1, promoting sonic hedgehog (SHH) signaling in the developing nervous system. GAS1 mutations in humans and animal models result in forebrain and craniofacial malformations, defects ascribed to a function for GAS1 in SHH signaling during early neurulation. Here, we confirm loss of SHH activity in the forebrain neuroepithelium in GAS1-deficient mice and in induced pluripotent stem cell-derived cell models of human neuroepithelial differentiation. However, our studies document that this defect can be attributed, at least in part, to a novel role for GAS1 in facilitating NOTCH signaling, which is essential to sustain a persistent SHH activity domain in the forebrain neuroepithelium. GAS1 directly binds NOTCH1, enhancing ligand-induced processing of the NOTCH1 intracellular domain, which drives NOTCH pathway activity in the developing forebrain. Our findings identify a unique role for GAS1 in integrating NOTCH and SHH signal reception in neuroepithelial cells, and they suggest that loss of GAS1-dependent NOTCH1 activation contributes to forebrain malformations in individuals carrying GAS1 mutations.

SUBMITTER: Marczenke M 

PROVIDER: S-EPMC8627604 | biostudies-literature |

REPOSITORIES: biostudies-literature

Similar Datasets

2021-10-26 | E-MTAB-10207 | biostudies-arrayexpress
| PRJEB43666 | ENA
| S-EPMC8604999 | biostudies-literature
| S-EPMC3432913 | biostudies-literature
| S-EPMC6876251 | biostudies-literature
| S-EPMC3653555 | biostudies-literature
2021-10-11 | GSE163505 | GEO
| S-EPMC4582185 | biostudies-literature
| S-EPMC2685963 | biostudies-literature
| S-EPMC4038327 | biostudies-literature