ZFIN ID: ZDB-PUB-170715-7
Genome-wide analysis of facial skeletal regionalization in zebrafish
Askary, A., Xu, P., Barske, L., Bay, M., Bump, P., Balczerski, B., Bonaguidi, M.A., Crump, J.G.
Date: 2017
Source: Development (Cambridge, England)   144(16): 2994-3005 (Journal)
Registered Authors: Balczerski, Bartosz, Barske, Lindsey, Crump, Gage DeKoeyer, Xu, Peng-Fei
Keywords: Bone, Cartilage, Cranial neural crest, Craniofacial, Dlx5a, Dorsoventral patterning, Edn1, Emx2, Endothelin, Fsta, Hand2, Jagged-Notch, Jaw, Mrrf, Skeleton, Zebrafish
Microarrays: GEO:GSE95812
MeSH Terms:
  • Animals
  • Body Patterning/genetics
  • Body Patterning/physiology
  • Branchial Region/embryology
  • Branchial Region/metabolism
  • Endothelin-1/genetics
  • Endothelin-1/metabolism
  • Flow Cytometry
  • Gene Expression Regulation, Developmental/genetics
  • Gene Expression Regulation, Developmental/physiology
  • In Situ Hybridization
  • Zebrafish/embryology*
  • Zebrafish/genetics*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed: 28705894 Full text @ Development
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 Endothelin 1 (Edn1) signaling in the intermediate joint-forming region, yet a surprisingly minor role in ventralmost 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.