期刊
DEVELOPMENT
卷 144, 期 16, 页码 2994-3005出版社
COMPANY OF BIOLOGISTS LTD
DOI: 10.1242/dev.151712
关键词
Craniofacial; Zebrafish; Jaw; Skeleton; Cartilage; Bone; Cranial neural crest; Dorsoventral patterning; Endothelin; Edn1; Jagged-Notch; Dlx5a; Hand2; Emx2; Fsta; Mrrf
资金
- National Institute of Dental and Craniofacial Research (NIDCR) [DE018405]
- National Institute of Neurological Disorders and Stroke [R00NS080913]
- Giannini Foundation
- NIDCR [K99DE026239]
- National Institute on Deafness and Other Communication Disorders [T32 DC009975]
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 covariance 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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据