Actin capping protein CAPZB regulates cell morphology, differentiation, and neural crest migration in craniofacial morphogenesis†.
Authors | |
Keywords | |
Abstract | CAPZB is an actin-capping protein that caps the growing end of F-actin and modulates the cytoskeleton and tethers actin filaments to the Z-line of the sarcomere in muscles. Whole-genome sequencing was performed on a subject with micrognathia, cleft palate and hypotonia that harbored a de novo, balanced chromosomal translocation that disrupts the CAPZB gene. The function of capzb was analyzed in the zebrafish model. capzb(-/-) mutants exhibit both craniofacial and muscle defects that recapitulate the phenotypes observed in the human subject. Loss of capzb affects cell morphology, differentiation and neural crest migration. Differentiation of both myogenic stem cells and neural crest cells requires capzb. During palate morphogenesis, defective cranial neural crest cell migration in capzb(-/-) mutants results in loss of the median cell population, creating a cleft phenotype. capzb is also required for trunk neural crest migration, as evident from melanophores disorganization in capzb(-/-) mutants. In addition, capzb over-expression results in embryonic lethality. Therefore, proper capzb dosage is important during embryogenesis, and regulates both cell behavior and tissue morphogenesis. |
Year of Publication | 2016
|
Journal | Hum Mol Genet
|
Volume | 25
|
Issue | 7
|
Pages | 1255-70
|
Date Published | 2016 Apr 01
|
ISSN | 1460-2083
|
URL | |
DOI | 10.1093/hmg/ddw006
|
PubMed ID | 26758871
|
PubMed Central ID | PMC4787901
|
Links | |
Grant list | P30 DK043351 / DK / NIDDK NIH HHS / United States
P01GM061354 / GM / NIGMS NIH HHS / United States
R00MH095867 / MH / NIMH NIH HHS / United States
P01 GM061354 / GM / NIGMS NIH HHS / United States
U01DE024443 / DE / NIDCR NIH HHS / United States
U01 DE024443 / DE / NIDCR NIH HHS / United States
P30 CA006516 / CA / NCI NIH HHS / United States
|