PUBLICATION
Actin capping protein CAPZB regulates cell morphology, differentiation, and neural crest migration in craniofacial morphogenesis
- Authors
- 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.
- ID
- ZDB-PUB-160114-5
- 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.
Citation
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. (2016) Actin capping protein CAPZB regulates cell morphology, differentiation, and neural crest migration in craniofacial morphogenesis. Human molecular genetics. 25(7):1255-70.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping