Skip Navigation



Human Molecular Genetics Advance Access published online on October 6, 2006
Human Molecular Genetics, doi:10.1093/hmg/ddl405
This Article
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
15/22/3293    most recent
ddl405v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Jiang, F.
Right arrow Articles by Herman, G. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Jiang, F.
Right arrow Articles by Herman, G. E.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2006. Published by Oxford University Press. All rights reserved
Received August 28, 2006
Revised September 27, 2006
Accepted September 27, 2006

Article

Analysis of Nsdhl Deficient Embryos Reveals a Role for Hedgehog Signaling in Early Placental Development

Fenglei Jiang 1 and Gail E. Herman 2 *

1 Center for Molecular and Human Genetics, Columbus Children's Research Institute and Department of Pediatrics, The Ohio State University, Columbus, OH 43205, USA
2 Center for Molecular and Human Genetics, Columbus Children's Research Institute and Department of Pediatrics, The Ohio State University, Columbus, 700 Children's Dr. Rm. W403, Columbus, OH 43205, USA

* To whom correspondence should be addressed.
Gail E. Herman, E-mail: hermang{at}ccri.net


  Abstract

The X-linked Nsdhl gene encodes a sterol dehydrogenase involved in cholesterol biosynthesis. Mutations in this gene cause the male lethal phenotypes in human CHILD syndrome and bare patches (Bpa) mice. Affected male embryos for several mutant Nsdhlalleles die in midgestation with a thin and poorly vascularized placental labyrinth. The timing and specific abnormalities noted suggest a defect in one or more developmental signaling pathways as a possible mechanism. Here we examined the possible involvement of the hedgehog signaling pathway in the placental pathology of Nsdhl mutants using a transgenic mouse line (Ptch1tm1Mps) that contains a lacZ reporter under the control of the promoter for Ptch1, the gene that encodes the major hedgehog receptor. We demonstrate expression of Ptch1in allantoic mesoderm of the placenta from wild type midgestation embryos. The evidence suggests that the signaling is induced by Indian hedgehog (IHH) that is produced by distal (ectoplacental) visceral endoderm cells that migrate into the allantoic mesoderm before embryonic day 10.0. Using a ubiquitously expressed, X-linked lacZ transgene that undergoes normal X-inactivation, we demonstrate that the placental defects in Nsdhl/ + female embryos are non-cell autonomous. Further, affected placentas from mutant NsdhlBpa-8H male embryos demonstrate markedly decreased or no Ptch1-lacZ staining and no migration of Ihh expressing cells into the developing placenta. These data strongly implicate the hedgehog signaling pathway in the pathogenesis of the placental defects in NSDHL deficiency and provide evidence for a role for the hedgehog pathway in the development of a functional mammalian placenta.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Hum Mol GenetHome page
D. Cunningham, T. Talabere, N. Bir, M. Kennedy, K. L. McBride, and G. E. Herman
Significant contributions of the extraembryonic membranes and maternal genotype to the placental pathology in heterozygous Nsdhl deficient female embryos
Hum. Mol. Genet., November 11, 2009; (2009) ddp502v2.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.