HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 282, Issue 26, 19071-19081, June 29, 2007

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 282/26/19071    most recent M607486200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map 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 Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Le, T. N. Articles by Eisenstat, D. D. Search for Related Content PubMed PubMed Citation Articles by Le, T. N. Articles by Eisenstat, D. D. Social Bookmarking                      What's this?

Dlx Homeobox Genes Promote Cortical Interneuron Migration from the Basal Forebrain by Direct Repression of the Semaphorin Receptor Neuropilin-2^*

Trung N. Le, Guoyan Du^¶, Mario Fonseca^¶, Qing-Ping Zhou^¶, Jeffrey T. Wigle^||, and David D. Eisenstat^¶**1

From the Departments of Biochemistry and Medical Genetics, ^¶Pediatrics and Child Health, ^**Human Anatomy and Cell Science, Manitoba Institute of Cell Biology, ^||St. Boniface General Hospital Research Centre, University of Manitoba, Winnipeg, Manitoba R3E 0V9, Canada

Dlx homeobox genes play an important role in vertebrate forebrain development. Dlx1/Dlx2 null mice die at birth with an abnormal cortical phenotype, including impaired differentiation and migration of GABAergic interneurons to the neocortex. However, the molecular basis for these defects downstream of loss of Dlx1/Dlx2 function is unknown. Neuropilin-2 (NRP-2) is a receptor for Class III semaphorins, which inhibit neuronal migration. Herein, we show that Neuropilin-2 is a specific DLX1 and DLX2 transcriptional target by applying chromatin immunoprecipitation to embryonic forebrain tissues. Both homeobox proteins repress Nrp-2 expression in vitro, confirming the functional significance of DLX binding. Furthermore, the homeodomain of DLX1 and DLX2 is necessary for DNA binding and this binding is essential for Dlx repression of Nrp-2 expression. Of importance, there is up-regulated and aberrant expression of NRP-2 in the forebrains of Dlx1/Dlx2 null mice. This is the first report that DLX1 or DLX2 can function as transcriptional repressors. Our data show that DLX proteins specifically mediate the repression of Neuropilin-2 in the developing forebrain. As well, our results support the hypothesis that down-regulation of Neuropilin-2 expression may facilitate tangential interneuron migration from the basal forebrain.

Received for publication, August 7, 2006 , and in revised form, January 12, 2007.

^* This work was supported by a Canadian Institutes of Health Research (CIHR) strategic training grant and Natural Sciences and Engineering Research Council graduate studentships (to T. N. L.), a Manitoba Institute of Child Health postdoctoral fellowship (to G. D.), a CIHR New Investigator Award (to J. T. W.), March of Dimes Birth Defects Foundation Basil O'Connor Starter Scholar Award 5-FY00-615 (to D. D. E.), and grants from the Foundation Fighting Blindness (Canada), CancerCare Manitoba Foundation, and Manitoba Medical Services Foundation (to D. D. E.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement"in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Figs. S1-S7.

¹ To whom correspondence should be addressed: Manitoba Inst. of Cell Biology, 675 McDermot Ave., Winnipeg, Manitoba R3E 0V9, Canada. Tel.: 204-787-1169; Fax: 204-787-2190; E-mail: eisensta{at}cc.umanitoba.ca.

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

This article has been cited by other articles:

				S. Nobrega-Pereira and O. Marin Transcriptional Control of Neuronal Migration in the Developing Mouse Brain Cereb Cortex, July 1, 2009; 19(suppl_1): i107 - i113. [Abstract] [Full Text] [PDF]

				G. Colasante, P. Collombat, V. Raimondi, D. Bonanomi, C. Ferrai, M. Maira, K. Yoshikawa, A. Mansouri, F. Valtorta, J. L. R. Rubenstein, et al. Arx Is a Direct Target of Dlx2 and Thereby Contributes to the Tangential Migration of GABAergic Interneurons J. Neurosci., October 15, 2008; 28(42): 10674 - 10686. [Abstract] [Full Text] [PDF]

				M. S. Brill, M. Snapyan, H. Wohlfrom, J. Ninkovic, M. Jawerka, G. S. Mastick, R. Ashery-Padan, A. Saghatelyan, B. Berninger, and M. Gotz A Dlx2- and Pax6-Dependent Transcriptional Code for Periglomerular Neuron Specification in the Adult Olfactory Bulb J. Neurosci., June 18, 2008; 28(25): 6439 - 6452. [Abstract] [Full Text] [PDF]

				J. de Melo, Q.-P. Zhou, Q. Zhang, S. Zhang, M. Fonseca, J. T. Wigle, and D. D. Eisenstat Dlx2 homeobox gene transcriptional regulation of Trkb neurotrophin receptor expression during mouse retinal development Nucleic Acids Res., February 11, 2008; 36(3): 872 - 884. [Abstract] [Full Text] [PDF]

				J. A. Dahl and P. Collas {micro}ChIP--a rapid micro chromatin immunoprecipitation assay for small cell samples and biopsies Nucleic Acids Res., February 11, 2008; 36(3): e15 - e15. [Abstract] [Full Text] [PDF]

				S. J. B. Butt, I. Cobos, J. Golden, N. Kessaris, V. Pachnis, and S. Anderson Transcriptional Regulation of Cortical Interneuron Development J. Neurosci., October 31, 2007; 27(44): 11847 - 11850. [Full Text] [PDF]