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A morpholino‐based screen to identify novel genes involved in craniofacial morphogenesis
Author(s) -
Melvin Vida Senkus,
Feng Weiguo,
HernandezLagunas Laura,
Artinger Kristin Bruk,
Williams Trevor
Publication year - 2013
Publication title -
developmental dynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.634
H-Index - 141
eISSN - 1097-0177
pISSN - 1058-8388
DOI - 10.1002/dvdy.23969
Subject(s) - morpholino , biology , zebrafish , craniofacial , gene knockdown , phenotype , gene , morphogenesis , craniofacial abnormality , genetics , microbiology and biotechnology , tbx1 , computational biology , gene expression , promoter
Background: The regulatory mechanisms underpinning facial development are conserved between diverse species. Therefore, results from model systems provide insight into the genetic causes of human craniofacial defects. Previously, we generated a comprehensive dataset examining gene expression during development and fusion of the mouse facial prominences. Here, we used this resource to identify genes that have dynamic expression patterns in the facial prominences, but for which only limited information exists concerning developmental function. Results: This set of ∼80 genes was used for a high‐throughput functional analysis in the zebrafish system using Morpholino gene knockdown technology. This screen revealed three classes of cranial cartilage phenotypes depending upon whether knockdown of the gene affected the neurocranium, viscerocranium, or both. The targeted genes that produced consistent phenotypes encoded proteins linked to transcription ( meis1, meis2a, tshz2, vgll4l ), signaling ( pkdcc, vlk, macc1, wu:fb16h09 ), and extracellular matrix function ( smoc2 ). The majority of these phenotypes were not altered by reduction of p53 levels, demonstrating that both p53‐dependent and ‐independent mechanisms were involved in the craniofacial abnormalities. Conclusions: This Morpholino‐based screen highlights new genes involved in development of the zebrafish craniofacial skeleton with wider relevance to formation of the face in other species, particularly mouse and human. Developmental Dynamics 242:817–831, 2013 . © 2013 Wiley Periodicals, Inc.