RT Journal Article SR Electronic T1 Genome-Wide Analysis of Facial Regionalization in Zebrafish JF bioRxiv FD Cold Spring Harbor Laboratory SP 114801 DO 10.1101/114801 A1 Amjad Askary A1 Pengfei Xu A1 Lindsey Barske A1 Maxwell Bay A1 Paul Bump A1 Bartosz Balczerski A1 Michael A. Bonaguidi A1 J. Gage Crump YR 2017 UL http://biorxiv.org/content/early/2017/03/07/114801.abstract AB 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 coregulated genes, with in situ hybridization confirming the domain-specific expression of novel genes. We then performed mutational analysis of a number of these genes, which 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 Ednl and points to novel candidates for craniofacial disorders.Summary Statement Using zebrafish to purify distinct groups of embryonic cells, Askary et al. have created a detailed map of how thousands of genes are deployed to shape the developing face.