Abstract:
:Craniofacial development is a highly conserved process that requires complex interactions between neural crest cells (NCCs) and pharyngeal tissues derived from all three germ layers. Signals emanating from the pharyngeal endoderm drive differentiation of NCCs into craniofacial cartilage, and disruption of this process underpins several human craniofacial defects (CFD). Here, we demonstrate that morpholino (MO)-mediated knockdown in zebrafish of the highly conserved transcription factor grainyhead-like 3 (grhl3), which is selectively expressed in the pharyngeal endoderm, leads to severe hypoplasia of the lower jaw cartilages. Phylogenetic analysis of conserved grhl-binding sites in gene regulatory regions identified endothelin-1 (edn1) as a putative direct grhl3 target gene, and this was confirmed by chromatin precipitation (ChIP) assays in zebrafish embryos. Injection of sub-phenotypic concentrations of MOs targeting both grhl3 and edn1 induced jaw abnormalities, and injection of edn1 mRNA into grhl3-morphants rescued both pharyngeal expression of the downstream effectors of edn1, and jaw cartilage formation. This study sheds new light on the role of endodermal endothelin-1 in vertebrate jaw development, and highlights potential new genetic defects that could underpin human CFD.
journal_name
Mech Devjournal_title
Mechanisms of developmentauthors
Dworkin S,Simkin J,Darido C,Partridge DD,Georgy SR,Caddy J,Wilanowski T,Lieschke GJ,Doggett K,Heath JK,Jane SMdoi
10.1016/j.mod.2014.05.005subject
Has Abstractpub_date
2014-08-01 00:00:00pages
77-90eissn
0925-4773issn
1872-6356pii
S0925-4773(14)00029-Xjournal_volume
133pub_type
杂志文章abstract::Unlike gap genes in the trunk region of Drosophila embryos, gap genes in the head were presumed not to regulate each other's transcription. Here, we show that in tailless (tll) loss-of-function mutants the empty spiracles (ems) expression domain in the head expands, whereas it retracts in tll gain-of-function embryos....
journal_title:Mechanisms of development
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journal_title:Mechanisms of development
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journal_title:Mechanisms of development
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journal_title:Mechanisms of development
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journal_title:Mechanisms of development
pub_type: 杂志文章
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journal_title:Mechanisms of development
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journal_title:Mechanisms of development
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journal_title:Mechanisms of development
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journal_title:Mechanisms of development
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journal_title:Mechanisms of development
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journal_title:Mechanisms of development
pub_type: 杂志文章
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journal_title:Mechanisms of development
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journal_title:Mechanisms of development
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journal_title:Mechanisms of development
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journal_title:Mechanisms of development
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journal_title:Mechanisms of development
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