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

doi:10.1093/hmg/ddw006

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

Division of Evolution, Infection and Genomics

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	1255-70
Number of pages	16
Journal	Human Molecular Genetics
Volume	25
Issue number	7
DOIs	https://doi.org/10.1093/hmg/ddw006
Publication status	Published - 1 Apr 2016

Keywords

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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10.1093/hmg/ddw006

Manchester Centre for Audiology and Deafness (ManCAD)
Munro, K. (PI), Millman, R. (PI), Lamb, W. (Support team), Dawes, P. (PI), Plack, C. (PI), Stone, M. (PI), Kluk-De Kort, K. (PI), Moore, D. (PI), Morton, C. (PI), Prendergast, G. (PI), Couth, S. (PI), Schlittenlacher, J. (PI), Chilton, H. (PI), Visram, A. (Researcher), Dillon, H. (PI), Guest, H. (Researcher), Heinrich, A. (PI), Jackson, I. (Researcher), Littlejohn, J. (Researcher), Jones, L. (PI), Lough, M. (Researcher), Morgan, R. (Researcher), Perugia, E. (Researcher), Roughley, A. (Researcher), Whiston, H. (Researcher), Wright, C. (Support team), Saunders, G. (PI), Kelly, C. (PI), Cross, H. (Researcher), Loughran, M. (Researcher), Hoseinabadi, R. (PI) & Vercammen, C. (PI)
Project: Research

Cite this

Mukherjee, K., Ishii, K., Pillalamarri, V., Kammin, T., Atkin, J. F., Hickey, S. E., Xi, Q. J., Zepeda, C. 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. https://doi.org/10.1093/hmg/ddw006

@article{e2b3845f59a84c6ca22365fbce50985b,

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.",

keywords = "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",

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

year = "2016",

month = apr,

day = "1",

doi = "10.1093/hmg/ddw006",

language = "English",

volume = "25",

pages = "1255--70",

journal = "Human Molecular Genetics",

issn = "0964-6906",

publisher = "Oxford University Press",

number = "7",

}

Mukherjee, K, Ishii, K, Pillalamarri, V, Kammin, T, Atkin, JF, Hickey, SE, Xi, QJ, Zepeda, CJ, Gusella, JF, Talkowski, ME, Morton, CC, Maas, RL & Liao, EC 2016, 'Actin capping protein CAPZB regulates cell morphology, differentiation, and neural crest migration in craniofacial morphogenesis†', Human Molecular Genetics, vol. 25, no. 7, pp. 1255-70. https://doi.org/10.1093/hmg/ddw006

TY - JOUR

T1 - Actin capping protein CAPZB regulates cell morphology, differentiation, and neural crest migration in craniofacial morphogenesis†

AU - Mukherjee, Kusumika

AU - Ishii, Kana

AU - Pillalamarri, Vamsee

AU - Kammin, Tammy

AU - Atkin, Joan F

AU - Hickey, Scott E

AU - Xi, Qiongchao J

AU - Zepeda, Cinthya J

AU - Gusella, James F

AU - Talkowski, Michael E

AU - Morton, Cynthia C

AU - Maas, Richard L

AU - Liao, Eric C

PY - 2016/4/1

Y1 - 2016/4/1

N2 - 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.

AB - 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.

KW - Animals

KW - CapZ Actin Capping Protein

KW - Cell Differentiation

KW - Cleft Palate

KW - Disease Models, Animal

KW - Female

KW - Head

KW - Humans

KW - Infant

KW - Micrognathism

KW - Morphogenesis

KW - Muscle Hypotonia

KW - Mutation

KW - Neural Crest

KW - Sequence Analysis, DNA

KW - Syndrome

KW - Zebrafish

KW - Case Reports

KW - Journal Article

KW - Research Support, N.I.H., Extramural

KW - Research Support, Non-U.S. Gov't

U2 - 10.1093/hmg/ddw006

DO - 10.1093/hmg/ddw006

M3 - Article

C2 - 26758871

SN - 0964-6906

VL - 25

SP - 1255

EP - 1270

JO - Human Molecular Genetics

JF - Human Molecular Genetics

IS - 7

ER -

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

Abstract

Keywords

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Manchester Centre for Audiology and Deafness (ManCAD)

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