QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) HTML Page - index.htslp Alert me when this article is cited 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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hori, K. Articles by Johnson, J. E. Search for Related Content PubMed PubMed Citation Articles by Hori, K. Articles by Johnson, J. E. Social Bookmarking                   What's this?

A nonclassical bHLH–Rbpj transcription factor complex is required for specification of GABAergic neurons independent of Notch signaling

¹ Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA; ² Max-Delbrück-Centrum for Molecular Medicine, 13125 Berlin-Buch, Germany; ³ Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA; ⁴ Department of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA; ⁵ Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA; ⁶ Vanderbilt Center for Stem Cell Biology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA

Neural networks are balanced by inhibitory and excitatory neuronal activity. The formation of these networks is initially generated through neuronal subtype specification controlled by transcription factors. The basic helix–loop–helix (bHLH) transcription factor Ptf1a is essential for the generation of GABAergic inhibitory neurons in the dorsal spinal cord, cerebellum, and retina. The transcription factor Rbpj is a transducer of the Notch signaling pathway that functions to maintain neural progenitor cells. Here we demonstrate Ptf1a and Rbpj interact in a complex that is required in vivo for specification of the GABAergic neurons, a function that cannot be substituted by the classical form of the bHLH heterodimer with E-protein or Notch signaling through Rbpj. We show that a mutant form of Ptf1a without the ability to bind Rbpj, while retaining its ability to interact with E-protein, is incapable of inducing GABAergic (Pax2)- and suppressing glutamatergic (Tlx3)-expressing cells in the chick and mouse neural tube. Moreover, we use an Rbpj conditional mutation to demonstrate that Rbpj function is essential for GABAergic specification, and that this function is independent of the Notch signaling pathway. Together, these findings demonstrate the requirement for a Ptf1a–Rbpj complex in controlling the balanced formation of inhibitory and excitatory neurons in the developing spinal cord, and point to a novel Notch-independent function for Rbpj in nervous system development.

[Keywords: Ptf1a; Notch; cerebellum; dorsal spinal cord; neuronal specification; bHLH transcription factor]]

Received May 23, 2007; revised version accepted November 14, 2007.

E-MAIL jane.johnson{at}utsouthwestern.edu; FAX (214) 648-1801.

Supplemental material is available at http://www.genesdev.org.

Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.1628008

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

This article has been cited by other articles:

				T. Masui, G. H. Swift, M. A. Hale, D. M. Meredith, J. E. Johnson, and R. J. MacDonald Transcriptional Autoregulation Controls Pancreatic Ptf1a Expression during Development and Adulthood Mol. Cell. Biol., September 1, 2008; 28(17): 5458 - 5468. [Abstract] [Full Text] [PDF]

				Y. Xu, C. Lopes, Y. Qian, Y. Liu, L. Cheng, M. Goulding, E. E. Turner, D. Lima, and Q. Ma Tlx1 and Tlx3 Coordinate Specification of Dorsal Horn Pain-Modulatory Peptidergic Neurons J. Neurosci., April 9, 2008; 28(15): 4037 - 4046. [Abstract] [Full Text] [PDF]