Myo1c is an unconventional myosin required for zebrafish glomerular development

Ehtesham Arif, Babita Kumari, Mark Wagner, Weibin Zhou, Lawrence B. Holzman, Deepak Nihalani

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

The targeting and organization of podocyte slit diaphragm proteins nephrin and neph1 is critical for development and maintenance of a functional glomerular filtration barrier. Myo1c is a non-muscle myosin motor protein that interacts directly with nephrin and neph1, and mediates their intracellular transport to the podocyte intercellular junction. Here we investigated the necessity of Myo1c in podocyte development using zebrafish as a model system. Immunofluorescence microscopy and in situ RNA hybridization analysis of zebrafish embryos showed that Myo1c is widely expressed in various tissues including the zebrafish glomerulus. Knockdown of the Myo1c gene in zebrafish using antisense morpholino derivatives resulted in an abnormal developmental phenotype that included pericardial edema and dilated renal tubules. Ultrastructural analysis of the glomerulus in Myo1c-depleted zebrafish showed abnormal podocyte morphology and absence of the slit diaphragm. Consistent with these observations, the glomerular filter permeability appeared altered in zebrafish in which Myo1c expression was attenuated. The specificity of Myo1c knockdown was confirmed by a rescue experiment in which co-injection of Myo1c morpholino derivatives with orthologous Myo1c mRNA prepared from mouse cDNA lessened phenotypic abnormalities including edema in Myo1c morphants. Thus, our results demonstrate that Myo1c is necessary for podocyte morphogenesis.

Original languageEnglish
Pages (from-to)1154-1165
Number of pages12
JournalKidney International
Volume84
Issue number6
DOIs
StatePublished - Dec 2013

Fingerprint

Zebrafish
Podocytes
Myosins
Morpholinos
Diaphragm
Edema
Glomerular Filtration Barrier
Gene Knockdown Techniques
Intercellular Junctions
Morphogenesis
Fluorescence Microscopy
In Situ Hybridization
Permeability
Proteins
Embryonic Structures
Complementary DNA
Maintenance
RNA
Phenotype
Kidney

Keywords

  • genetics and development
  • glomerular disease
  • podocyte
  • proteinuria
  • renal development
  • renal dysfunction

ASJC Scopus subject areas

  • Nephrology

Cite this

Myo1c is an unconventional myosin required for zebrafish glomerular development. / Arif, Ehtesham; Kumari, Babita; Wagner, Mark; Zhou, Weibin; Holzman, Lawrence B.; Nihalani, Deepak.

In: Kidney International, Vol. 84, No. 6, 12.2013, p. 1154-1165.

Research output: Contribution to journalArticle

Arif, E, Kumari, B, Wagner, M, Zhou, W, Holzman, LB & Nihalani, D 2013, 'Myo1c is an unconventional myosin required for zebrafish glomerular development', Kidney International, vol. 84, no. 6, pp. 1154-1165. https://doi.org/10.1038/ki.2013.201
Arif, Ehtesham ; Kumari, Babita ; Wagner, Mark ; Zhou, Weibin ; Holzman, Lawrence B. ; Nihalani, Deepak. / Myo1c is an unconventional myosin required for zebrafish glomerular development. In: Kidney International. 2013 ; Vol. 84, No. 6. pp. 1154-1165.
@article{0ec4003caa2645c0be96134db8cba797,
title = "Myo1c is an unconventional myosin required for zebrafish glomerular development",
abstract = "The targeting and organization of podocyte slit diaphragm proteins nephrin and neph1 is critical for development and maintenance of a functional glomerular filtration barrier. Myo1c is a non-muscle myosin motor protein that interacts directly with nephrin and neph1, and mediates their intracellular transport to the podocyte intercellular junction. Here we investigated the necessity of Myo1c in podocyte development using zebrafish as a model system. Immunofluorescence microscopy and in situ RNA hybridization analysis of zebrafish embryos showed that Myo1c is widely expressed in various tissues including the zebrafish glomerulus. Knockdown of the Myo1c gene in zebrafish using antisense morpholino derivatives resulted in an abnormal developmental phenotype that included pericardial edema and dilated renal tubules. Ultrastructural analysis of the glomerulus in Myo1c-depleted zebrafish showed abnormal podocyte morphology and absence of the slit diaphragm. Consistent with these observations, the glomerular filter permeability appeared altered in zebrafish in which Myo1c expression was attenuated. The specificity of Myo1c knockdown was confirmed by a rescue experiment in which co-injection of Myo1c morpholino derivatives with orthologous Myo1c mRNA prepared from mouse cDNA lessened phenotypic abnormalities including edema in Myo1c morphants. Thus, our results demonstrate that Myo1c is necessary for podocyte morphogenesis.",
keywords = "genetics and development, glomerular disease, podocyte, proteinuria, renal development, renal dysfunction",
author = "Ehtesham Arif and Babita Kumari and Mark Wagner and Weibin Zhou and Holzman, {Lawrence B.} and Deepak Nihalani",
year = "2013",
month = "12",
doi = "10.1038/ki.2013.201",
language = "English",
volume = "84",
pages = "1154--1165",
journal = "Kidney International",
issn = "0085-2538",
publisher = "Nature Publishing Group",
number = "6",

}

TY - JOUR

T1 - Myo1c is an unconventional myosin required for zebrafish glomerular development

AU - Arif, Ehtesham

AU - Kumari, Babita

AU - Wagner, Mark

AU - Zhou, Weibin

AU - Holzman, Lawrence B.

AU - Nihalani, Deepak

PY - 2013/12

Y1 - 2013/12

N2 - The targeting and organization of podocyte slit diaphragm proteins nephrin and neph1 is critical for development and maintenance of a functional glomerular filtration barrier. Myo1c is a non-muscle myosin motor protein that interacts directly with nephrin and neph1, and mediates their intracellular transport to the podocyte intercellular junction. Here we investigated the necessity of Myo1c in podocyte development using zebrafish as a model system. Immunofluorescence microscopy and in situ RNA hybridization analysis of zebrafish embryos showed that Myo1c is widely expressed in various tissues including the zebrafish glomerulus. Knockdown of the Myo1c gene in zebrafish using antisense morpholino derivatives resulted in an abnormal developmental phenotype that included pericardial edema and dilated renal tubules. Ultrastructural analysis of the glomerulus in Myo1c-depleted zebrafish showed abnormal podocyte morphology and absence of the slit diaphragm. Consistent with these observations, the glomerular filter permeability appeared altered in zebrafish in which Myo1c expression was attenuated. The specificity of Myo1c knockdown was confirmed by a rescue experiment in which co-injection of Myo1c morpholino derivatives with orthologous Myo1c mRNA prepared from mouse cDNA lessened phenotypic abnormalities including edema in Myo1c morphants. Thus, our results demonstrate that Myo1c is necessary for podocyte morphogenesis.

AB - The targeting and organization of podocyte slit diaphragm proteins nephrin and neph1 is critical for development and maintenance of a functional glomerular filtration barrier. Myo1c is a non-muscle myosin motor protein that interacts directly with nephrin and neph1, and mediates their intracellular transport to the podocyte intercellular junction. Here we investigated the necessity of Myo1c in podocyte development using zebrafish as a model system. Immunofluorescence microscopy and in situ RNA hybridization analysis of zebrafish embryos showed that Myo1c is widely expressed in various tissues including the zebrafish glomerulus. Knockdown of the Myo1c gene in zebrafish using antisense morpholino derivatives resulted in an abnormal developmental phenotype that included pericardial edema and dilated renal tubules. Ultrastructural analysis of the glomerulus in Myo1c-depleted zebrafish showed abnormal podocyte morphology and absence of the slit diaphragm. Consistent with these observations, the glomerular filter permeability appeared altered in zebrafish in which Myo1c expression was attenuated. The specificity of Myo1c knockdown was confirmed by a rescue experiment in which co-injection of Myo1c morpholino derivatives with orthologous Myo1c mRNA prepared from mouse cDNA lessened phenotypic abnormalities including edema in Myo1c morphants. Thus, our results demonstrate that Myo1c is necessary for podocyte morphogenesis.

KW - genetics and development

KW - glomerular disease

KW - podocyte

KW - proteinuria

KW - renal development

KW - renal dysfunction

UR - http://www.scopus.com/inward/record.url?scp=84888640137&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84888640137&partnerID=8YFLogxK

U2 - 10.1038/ki.2013.201

DO - 10.1038/ki.2013.201

M3 - Article

VL - 84

SP - 1154

EP - 1165

JO - Kidney International

JF - Kidney International

SN - 0085-2538

IS - 6

ER -