QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

First published online January 11, 2008
doi: 10.1242/10.1242/dev.013763

This Article Figures Only Full Text Full Text (PDF) Supplementary Material Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Pickett, E. A. Articles by Tallquist, M. D. Search for Related Content PubMed PubMed Citation Articles by Pickett, E. A. Articles by Tallquist, M. D. Social Bookmarking                         What's this?

Disruption of PDGFR-initiated PI3K activation and migration of somite derivatives leads to spina bifida

Department of Molecular Biology, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, USA.

^* Author for correspondence (e-mail: michelle.tallquist{at}utsouthwestern.edu)

Accepted 2 November 2007

Spina bifida, or failure of the vertebrae to close at the midline, is a common congenital malformation in humans that is often synonymous with neural tube defects (NTDs). However, it is likely that other etiologies exist. Genetic disruption of platelet-derived growth factor receptor (PDGFR) results in spina bifida, but the underlying mechanism has not been identified. To elucidate the cause of this birth defect in PDGFR mutant embryos, we examined the developmental processes involved in vertebrae formation. Exposure of chick embryos to the PDGFR inhibitor imatinib mesylate resulted in spina bifida in the absence of NTDs. We next examined embryos with a tissue-specific deletion of the receptor. We found that loss of the receptor from chondrocytes did not recapitulate the spina bifida phenotype. By contrast, loss of the receptor from all sclerotome and dermatome derivatives or disruption of PDGFR-driven phosphatidyl-inositol 3' kinase (PI3K) activity resulted in spina bifida. Furthermore, we identified a migration defect in the sclerotome as the cause of the abnormal vertebral development. We found that primary cells from these mice exhibited defects in PAK1 activation and paxillin localization. Taken together, these results indicate that PDGFR downstream effectors, especially PI3K, are essential for cell migration of a somite-derived dorsal mesenchyme and disruption of receptor signaling in these cells leads to spina bifida.

Key words: Spina bifida, PDGF, PI3 kinase, Cell migration, S6K1, PAK1, Mouse, Chick

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				X. Yang, H. Chrisman, and C. J. Weijer PDGF signalling controls the migration of mesoderm cells during chick gastrulation by regulating N-cadherin expression Development, November 1, 2008; 135(21): 3521 - 3530. [Abstract] [Full Text] [PDF]

				D. E. Clouthier, J. Gray, and K. B. Artinger Micromanaging Palate Development Speech Science and Orofacial Disorders, October 1, 2008; 18(2): 62 - 72. [Abstract] [Full Text] [PDF]