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Neph3 associates with regulation of glomerular and neural development in zebrafish.
MedLine Citation:
PMID:  22099175     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
Neph3 (filtrin) is a membrane protein expressed in the glomerular epithelial cells (podocytes), but its role in the glomerulus is still largely unknown. To characterize the function of Neph3 in the glomerulus, we employed the zebrafish as a model system. Here we show that the expression of neph3 in pronephros starts before the onset of nephrin and podocin expression, peaks when the nephron primordium differentiates into glomerulus and tubulus, and is then downregulated upon glomerular maturation. By histology, we found that neph3 is specifically expressed in pronephric podocytes at 36hpf. Furthermore, disruption of neph3 expression by antisense morpholino oligonucleotides results in distorted body curvature and transient pericardial edema, the latter likely reflecting perturbation of glomerular osmoregulatory function. Histological analysis of neph3 morphants reveals altered glomerular morphology and dilated pronephric tubules. The phenotype of neph3 morphants, curved body and pericardial edema, is rescued by wild-type zebrafish neph3 mRNA. In addition to glomerulus, neph3 is highly expressed in the developing brain and specific regions of mature midbrain and hindbrain. In line with this, neph3 morphants show aberrant brain morphology. Collectively, the expression of neph3 in glomerulus and brain together with the morphant phenotype imply that neph3 is a pleiotropic gene active during distinct stages of tissue differentiation and associates directly in the regulation of both glomerular and neural development.
Authors:
Hong Wang; Sanna Lehtonen; Yu-Chia Chen; Eija Heikkilä; Pertti Panula; Harry Holthöfer
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Publication Detail:
Type:  Journal Article     Date:  2011-10-06
Journal Detail:
Title:  Differentiation; research in biological diversity     Volume:  83     ISSN:  1432-0436     ISO Abbreviation:  Differentiation     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2011-11-21     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0401650     Medline TA:  Differentiation     Country:  England    
Other Details:
Languages:  eng     Pagination:  38-46     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 International Society of Differentiation. Published by Elsevier B.V. All rights reserved.
Affiliation:
Department of Bacteriology and Immunology, Haartman Institute, Haartmaninkatu 3, P.O. Box 21, PL21, FIN-00014, University of Helsinki, Finland; Department of Biological and Environmental Science, P.O. Box 35, FIN-40014, University of Jyväskylä, Finland.
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