Jagged-Notch signaling ensures dorsal skeletal identity in the vertebrate face.

Development
Authors
Keywords
Abstract

The development of the vertebrate face relies on the regionalization of neural crest-derived skeletal precursors along the dorsoventral (DV) axis. Here we show that Jagged-Notch signaling ensures dorsal identity within the hyoid and mandibular components of the facial skeleton by repressing ventral fates. In a genetic screen in zebrafish, we identified a loss-of-function mutation in jagged 1b (jag1b) that results in dorsal expansion of ventral gene expression and partial transformation of the dorsal hyoid skeleton to a ventral morphology. Conversely, misexpression of human jagged 1 (JAG1) represses ventral gene expression and dorsalizes the ventral hyoid and mandibular skeletons. We further show that jag1b is expressed specifically in dorsal skeletal precursors, where it acts through the Notch2 receptor to activate hey1 expression. Whereas Jagged-Notch positive feedback propagates jag1b expression throughout the dorsal domain, Endothelin 1 (Edn1) inhibits jag1b and hey1 expression in the ventral domain. Strikingly, reduction of Jag1b or Notch2 function partially rescues the ventral defects of edn1 mutants, indicating that Edn1 promotes facial skeleton development in part by inhibiting Jagged-Notch signaling in ventral skeletal precursors. Together, these results indicate a novel function of Jagged-Notch signaling in ensuring dorsal identity within broad fields of facial skeletal precursors.

Year of Publication
2010
Journal
Development
Volume
137
Issue
11
Pages
1843-52
Date Published
2010 Jun
ISSN
1477-9129
DOI
10.1242/dev.049056
PubMed ID
20431122
PubMed Central ID
PMC2867320
Links
Grant list
R01 DE018405 / DE / NIDCR NIH HHS / United States
HD22486 / HD / NICHD NIH HHS / United States
P01 HD022486 / HD / NICHD NIH HHS / United States
R01 DE013834 / DE / NIDCR NIH HHS / United States
DE13834 / DE / NIDCR NIH HHS / United States