Document Detail


Activation of the Hedgehog pathway in the mouse fetal ovary leads to ectopic appearance of fetal Leydig cells and female pseudohermaphroditism.
MedLine Citation:
PMID:  19268447     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Proper cell fate determination in mammalian gonads is critical for the establishment of sexual identity. The Hedgehog (Hh) pathway has been implicated in cell fate decision for various organs, including gonads. Desert Hedgehog (Dhh), one of the three mammalian Hh genes, has been implicated with other genes in the establishment of mouse fetal Leydig cells. To investigate whether Hh alone is sufficient to induce fetal Leydig cell differentiation, we ectopically activated the Hh pathway in Steroidogenic factor 1 (SF1)-positive somatic cell precursors of fetal ovaries. Hh activation transformed SF1-positive somatic ovarian cells into functional fetal Leydig cells. These ectopic fetal Leydig cells produced androgens and insulin-like growth factor 3 (INLS3) that cause virilization of female embryos and ovarian descent. However, the female reproductive system remained intact, indicating a typical example of female pseudohermaphroditism. The appearance of fetal Leydig cells was a direct consequence of Hh activation as evident by the absence of other testicular components in the affected ovary. This study provides not only insights into mechanisms of cell lineage specification in gonads, but also a model to understand defects in sexual differentiation.
Authors:
Ivraym B Barsoum; Nathan C Bingham; Keith L Parker; Joan S Jorgensen; Humphrey H-C Yao
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2009-03-03
Journal Detail:
Title:  Developmental biology     Volume:  329     ISSN:  1095-564X     ISO Abbreviation:  Dev. Biol.     Publication Date:  2009 May 
Date Detail:
Created Date:  2009-04-17     Completed Date:  2009-05-19     Revised Date:  2010-09-22    
Medline Journal Info:
Nlm Unique ID:  0372762     Medline TA:  Dev Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  96-103     Citation Subset:  IM    
Affiliation:
Department of Cell and Developmental Biology, University of Illinois at Urbana-Champaign, IL 61820, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Differentiation / genetics
Embryo, Mammalian / cytology,  metabolism
Female
Fetus* / cytology,  metabolism
Hedgehog Proteins / genetics,  metabolism*
Immunohistochemistry
In Situ Hybridization
Leydig Cells / cytology,  metabolism*,  physiology
Male
Mice
Mice, Transgenic
Ovary / metabolism*
Pseudohermaphroditism / genetics,  metabolism*
Sex Differentiation
Signal Transduction / genetics
Grant Support
ID/Acronym/Agency:
DK54480/DK/NIDDK NIH HHS; HD046743/HD/NICHD NIH HHS; HD46861/HD/NICHD NIH HHS; HD48911/HD/NICHD NIH HHS; R01 HD046861-05/HD/NICHD NIH HHS
Chemical
Reg. No./Substance:
0/Hedgehog Proteins
Comments/Corrections

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