ZFIN ID: ZDB-PUB-160114-5
Actin capping protein CAPZB regulates cell morphology, differentiation, and neural crest migration in craniofacial morphogenesis
Mukherjee, K., Ishii, K., Pillalamarri, V., Kammin, T., Atkin, J.F., Hickey, S.E., Xi, Q.J., Gusella, J.F., Talkowski, M.E., Morton, C.C., Maas, R.L., Liao, E.C.
Date: 2016
Source: Human molecular genetics   25(7): 1255-70 (Journal)
Registered Authors: Liao, Eric
Keywords: none
MeSH Terms:
  • Animals
  • CapZ Actin Capping Protein/genetics*
  • Cell Differentiation*
  • Cleft Palate/genetics
  • Cleft Palate/metabolism
  • Disease Models, Animal
  • Female
  • Head/embryology*
  • Head/physiology
  • Humans
  • Infant
  • Micrognathism/genetics
  • Micrognathism/metabolism
  • Morphogenesis*
  • Muscle Hypotonia/genetics
  • Muscle Hypotonia/metabolism
  • Mutation
  • Neural Crest/embryology*
  • Neural Crest/metabolism
  • Neural Crest/physiology
  • Sequence Analysis, DNA
  • Syndrome
  • Zebrafish/embryology
  • Zebrafish/metabolism
  • Zebrafish/physiology
PubMed: 26758871 Full text @ Hum. Mol. Genet.
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.