title: Actin capping protein CAPZB regulates cell morphology, differentiation, and neural crest migration in craniofacial morphogenesis†.
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.
authors.affiliation: Center for Regenerative Medicine, Division of Plastic and Reconstructive Surgery, Harvard Medical School, Harvard University, Boston, MA 02114, USA.
authors.forename: Kusumika
authors.initials: K
authors.lastname: Mukherjee
authors.affiliation: Center for Regenerative Medicine, Division of Plastic and Reconstructive Surgery, Department of Biochemistry and Molecular Biology, Nippon Medical School, Bunkyo, Tokyo 113-0022, Japan, Harvard Medical School, Harvard University, Boston, MA 02114, USA.
authors.forename: Kana
authors.initials: K
authors.lastname: Ishii
authors.affiliation: Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA 02114, USA.
authors.forename: Vamsee
authors.initials: V
authors.lastname: Pillalamarri
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Biology.
authors.forename: Tammy
authors.initials: T
authors.lastname: Kammin
authors.affiliation: Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH 43210, USA, Division of Molecular and Human Genetics, Nationwide Children's Hospital, Columbus, OH 43205, USA.
authors.forename: Joan F
authors.initials: JF
authors.lastname: Atkin
authors.affiliation: Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH 43210, USA, Division of Molecular and Human Genetics, Nationwide Children's Hospital, Columbus, OH 43205, USA.
authors.forename: Scott E
authors.initials: SE
authors.lastname: Hickey
authors.affiliation: Department of Medicine, Division of Genetics, Brigham and Women's Hospital, Boston, MA 02115, USA, Harvard Medical School, Harvard University, Boston, MA 02114, USA.
authors.forename: Qiongchao J
authors.initials: QJ
authors.lastname: Xi
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Biology.
authors.forename: Cinthya J
authors.initials: CJ
authors.lastname: Zepeda
authors.affiliation: Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA 02114, USA, Harvard Medical School, Harvard University, Boston, MA 02114, USA.
authors.forename: James F
authors.initials: JF
authors.lastname: Gusella
authors.affiliation: Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA 02114, USA, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA and Harvard Medical School, Harvard University, Boston, MA 02114, USA.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Talkowski
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Biology, Department of Pathology and Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA and Harvard Medical School, Harvard University, Boston, MA 02114, USA.
authors.forename: Cynthia C
authors.initials: CC
authors.lastname: Morton
authors.affiliation: Department of Medicine, Division of Genetics, Brigham and Women's Hospital, Boston, MA 02115, USA, Harvard Medical School, Harvard University, Boston, MA 02114, USA.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Maas
authors.affiliation: Center for Regenerative Medicine, Division of Plastic and Reconstructive Surgery, Harvard Medical School, Harvard University, Boston, MA 02114, USA cliao@partners.org.
authors.forename: Eric C
authors.initials: EC
authors.lastname: Liao
mesh_terms: D000818:Animals; D051347:CapZ Actin Capping Protein / Q000235:genetics*; D002454:Cell Differentiation; D002972:Cleft Palate / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D006257:Head / Q000196:embryology* / Q000502:physiology; D006801:Humans; D007223:Infant; D008844:Micrognathism / Q000235:genetics / Q000378:metabolism; D009024:Morphogenesis; D009123:Muscle Hypotonia / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D009432:Neural Crest / Q000196:embryology* / Q000378:metabolism / Q000502:physiology; D017422:Sequence Analysis, DNA; D013577:Syndrome; D015027:Zebrafish / Q000196:embryology / Q000378:metabolism / Q000502:physiology
chemical_list: D051347:CapZ Actin Capping Protein