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

First published online January 25, 2008
doi: 10.1242/10.1242/dev.013276

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 Related articles in Development 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 Iulianella, A. Articles by Trainor, P. A. Search for Related Content PubMed PubMed Citation Articles by Iulianella, A. Articles by Trainor, P. A. Social Bookmarking                         What's this?

Cux2 (Cutl2) integrates neural progenitor development with cell-cycle progression during spinal cord neurogenesis

¹ Stowers Institute for Medical Research, 1000 E. 50th Street, Kansas City, MO 64110, USA.
² Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, KS 66160, USA.

^* Author for correspondence (e-mail: pat{at}stowers-institute.org)

Accepted 3 December 2007

Neurogenesis requires the coordination of neural progenitor proliferation and differentiation with cell-cycle regulation. However, the mechanisms coordinating these distinct cellular activities are poorly understood. Here we demonstrate for the first time that a Cut-like homeodomain transcription factor family member, Cux2 (Cutl2), regulates cell-cycle progression and development of neural progenitors. Cux2 loss-of-function mouse mutants exhibit smaller spinal cords with deficits in neural progenitor development as well as in neuroblast and interneuron differentiation. These defects correlate with reduced cell-cycle progression of neural progenitors coupled with diminished Neurod and p27^Kip1 activity. Conversely, in Cux2 gain-of-function transgenic mice, the spinal cord is enlarged in association with enhanced neuroblast formation and neuronal differentiation, particularly with respect to interneurons. Furthermore, Cux2 overexpression induces high levels of Neurod and p27^Kip1. Mechanistically, we discovered through chromatin immunoprecipitation assays that Cux2 binds both the Neurod and p27^Kip1 promoters in vivo, indicating that these interactions are direct. Our results therefore show that Cux2 functions at multiple levels during spinal cord neurogenesis. Cux2 initially influences cell-cycle progression in neural progenitors but subsequently makes additional inputs through Neurod and p27^Kip1 to regulate neuroblast formation, cell-cycle exit and cell-fate determination. Thus our work defines novel roles for Cux2 as a transcription factor that integrates cell-cycle progression with neural progenitor development during spinal cord neurogenesis.

Key words: Cut-like, Cux, Spinal cord, Neurogenesis, Interneurons, Motoneurons, Neurod1, p27^Kip1, Cell cycle, Mouse

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

Related articles in Development:

Neurogenesis gets the cux

Development 2008 135: e405. [Full Text]  

This article has been cited by other articles:

				A. Iulianella, M. Sharma, G. B. Vanden Heuvel, and P. A. Trainor Cux2 functions downstream of Notch signaling to regulate dorsal interneuron formation in the spinal cord Development, July 15, 2009; 136(14): 2329 - 2334. [Abstract] [Full Text] [PDF]