Actin capping protein CAPZB regulates cell morphology, differentiation, and neural crest migration in craniofacial morphogenesis†

Kusumika Mukherjee, Kana Ishii, Vamsee Pillalamarri, Tammy Kammin, Joan F Atkin, Scott E Hickey, Qiongchao J Xi, Cinthya J Zepeda, James F Gusella, Michael E Talkowski, Cynthia C Morton, Richard L Maas, Eric C Liao

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)1255-70
Number of pages16
JournalHuman Molecular Genetics
Issue number7
Publication statusPublished - 1 Apr 2016


  • Animals
  • CapZ Actin Capping Protein
  • Cell Differentiation
  • Cleft Palate
  • Disease Models, Animal
  • Female
  • Head
  • Humans
  • Infant
  • Micrognathism
  • Morphogenesis
  • Muscle Hypotonia
  • Mutation
  • Neural Crest
  • Sequence Analysis, DNA
  • Syndrome
  • Zebrafish
  • Case Reports
  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't


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