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Genome-wide analysis of facial skeletal regionalization in zebrafish

Authors :
Maxwell Bay
Michael A. Bonaguidi
Amjad Askary
Bartosz Balczerski
J. Gage Crump
Pengfei Xu
Paul A. Bump
Lindsey Barske
Source :
Development (Cambridge, England). 144(16)
Publication Year :
2017

Abstract

Patterning of the facial skeleton involves the precise deployment of thousands of genes in distinct regions of the pharyngeal arches. Despite the significance for craniofacial development, how genetic programs drive this regionalization remains incompletely understood. Here we use combinatorial labeling of zebrafish cranial neural crest-derived cells (CNCCs) to define global gene expression along the dorsoventral axis of the developing arches. Intersection of region-specific transcriptomes with expression changes in response to signaling perturbations demonstrates complex roles for Endothelin1 (Edn1) signaling in the intermediate joint-forming region, yet a surprisingly minor role in ventral-most regions. Analysis of co-variance across multiple sequencing experiments further reveals clusters of co-regulated genes, with in situ hybridization confirming the domain-specific expression of novel genes. We then created loss-of-function alleles for 12 genes and uncovered antagonistic functions of two new Edn1 targets, follistatin a (fsta) and emx2, in regulating cartilaginous joints in the hyoid arch. Our unbiased discovery and functional analysis of genes with regional expression in zebrafish arch CNCCs reveals complex regulation by Edn1 and points to novel candidates for craniofacial disorders.

Details

ISSN :
14779129
Volume :
144
Issue :
16
Database :
OpenAIRE
Journal :
Development (Cambridge, England)
Accession number :
edsair.doi.dedup.....3ade608527e2bd6f6dc263e1f20f169e