dc.contributor.author
Marczenke, Maike
dc.contributor.author
Sunaga-Franze, Daniele Yumi
dc.contributor.author
Popp, Oliver
dc.contributor.author
Althaus, Irene W.
dc.contributor.author
Sauer, Sascha
dc.contributor.author
Mertins, Philipp
dc.contributor.author
Christ, Annabel
dc.contributor.author
Allen, Benjamin L.
dc.contributor.author
Willnow, Thomas E.
dc.date.accessioned
2022-01-11T10:25:26Z
dc.date.available
2022-01-11T10:25:26Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/33439
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-33160
dc.description.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.
en
dc.format.extent
14 Seiten
dc.rights.uri
https://creativecommons.org/licenses/by/4.0/
dc.subject
Forebrain organizer region
en
dc.subject
Holoprosencephaly
en
dc.subject
NOTCH intracellular domain
en
dc.subject
Neuroepithelial precursor cells
en
dc.subject
HH co-receptors
en
dc.subject.ddc
500 Naturwissenschaften und Mathematik::570 Biowissenschaften; Biologie::570 Biowissenschaften; Biologie
dc.title
GAS1 is required for NOTCH-dependent facilitation of SHH signaling in the ventral forebrain neuroepithelium
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation.articlenumber
dev200080
dcterms.bibliographicCitation.doi
10.1242/dev.200080
dcterms.bibliographicCitation.journaltitle
Development
dcterms.bibliographicCitation.number
21
dcterms.bibliographicCitation.volume
148
dcterms.bibliographicCitation.url
https://doi.org/10.1242/dev.200080
refubium.affiliation
Biologie, Chemie, Pharmazie
refubium.resourceType.isindependentpub
no
dcterms.accessRights.openaire
open access
dcterms.isPartOf.eissn
1477-9129
refubium.resourceType.provider
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