Document Detail


Hox10 genes function in kidney development in the differentiation and integration of the cortical stroma.
MedLine Citation:
PMID:  21858105     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Organogenesis requires the differentiation and integration of distinct populations of cells to form a functional organ. In the kidney, reciprocal interactions between the ureter and the nephrogenic mesenchyme are required for organ formation. Additionally, the differentiation and integration of stromal cells are also necessary for the proper development of this organ. Much remains to be understood regarding the origin of cortical stromal cells and the pathways involved in their formation and function. By generating triple mutants in the Hox10 paralogous group genes, we demonstrate that Hox10 genes play a critical role in the developing kidney. Careful examination of control kidneys show that Foxd1-expressing stromal precursor cells are first observed in a cap-like pattern anterior to the metanephric mesenchyme and these cells subsequently integrate posteriorly into the kidney periphery as development proceeds. While the initial cap-like pattern of Foxd1-expressing cortical stromal cells is unaffected in Hox10 mutants, these cells fail to become properly integrated into the kidney, and do not differentiate to form the kidney capsule. Consistent with loss of cortical stromal cell function, Hox10 mutant kidneys display reduced and aberrant ureter branching, decreased nephrogenesis. These data therefore provide critical novel insights into the cellular and genetic mechanisms governing cortical cell development during kidney organogenesis. These results, combined with previous evidence demonstrating that Hox11 genes are necessary for patterning the metanephric mesenchyme, support a model whereby distinct populations in the nephrogenic cord are regulated by unique Hox codes, and that differential Hox function along the AP axis of the nephrogenic cord is critical for the differentiation and integration of these cell types during kidney organogenesis.
Authors:
Alisha R Yallowitz; Steven M Hrycaj; Kieran M Short; Ian M Smyth; Deneen M Wellik
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-08-16
Journal Detail:
Title:  PloS one     Volume:  6     ISSN:  1932-6203     ISO Abbreviation:  PLoS ONE     Publication Date:  2011  
Date Detail:
Created Date:  2011-08-22     Completed Date:  2012-02-15     Revised Date:  2013-06-27    
Medline Journal Info:
Nlm Unique ID:  101285081     Medline TA:  PLoS One     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e23410     Citation Subset:  IM    
Affiliation:
Department of Internal Medicine, Division of Molecular Medicine and Genetics University of Michigan, Ann Arbor, Michigan, United States of America.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Differentiation / genetics,  physiology*
Embryo, Mammalian / embryology,  metabolism
Forkhead Transcription Factors / genetics,  metabolism,  physiology
Gene Expression Regulation, Developmental
Homeodomain Proteins / genetics,  metabolism,  physiology*
Immunohistochemistry
In Situ Hybridization
Kidney / cytology,  embryology*,  metabolism
Kidney Cortex / cytology,  embryology*,  metabolism
Mice
Mice, Knockout
Organ Culture Techniques
Organogenesis / genetics,  physiology
Stromal Cells / cytology,  metabolism
Time Factors
Transcription Factors / genetics,  metabolism,  physiology*
Ureter / embryology,  metabolism
Grant Support
ID/Acronym/Agency:
5 P30 CA46592/CA/NCI NIH HHS; DK071929/DK/NIDDK NIH HHS; T32-DK065517/DK/NIDDK NIH HHS; T32-HD007505/HD/NICHD NIH HHS
Chemical
Reg. No./Substance:
0/Forkhead Transcription Factors; 0/Foxd1 protein, mouse; 0/Homeodomain Proteins; 0/Transcription Factors; 0/Vsx2 protein, mouse
Comments/Corrections

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