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

First published online December 7, 2008
doi: 10.1242/10.1242/dev.030064

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 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 Etchberger, J. F. Articles by Hobert, O. Search for Related Content PubMed Articles by Etchberger, J. F. Articles by Hobert, O. Social Bookmarking                         What's this?

Cis-regulatory mechanisms of left/right asymmetric neuron-subtype specification in C. elegans

Howard Hughes Medical Institute, Department of Biochemistry and Molecular Biophysics, Columbia University Medical Center, 701 West 168th Street, New York, NY 10032, USA.

^* Author for correspondence (e-mail: or38{at}columbia.edu)

Accepted 22 October 2008

Anatomically and functionally defined neuron types are sometimes further classified into individual subtypes based on unique functional or molecular properties. To better understand how developmental programs controlling neuron type specification are mechanistically linked to programs controlling neuronal subtype specification, we have analyzed a neuronal subtype specification program that occurs across the left/right axis in the nervous system of the nematode C. elegans. A terminal selector transcription factor, CHE-1, is required for the specification of the ASE neuron class, and a gene regulatory feedback loop of transcription factors and miRNAs is required to diversify the two ASE neurons into an asymmetric left and right subtype (ASEL and ASER). However, the link between the CHE-1-dependent ASE neuron class specification and the ensuing left-right subtype specification program is poorly understood. We show here that CHE-1 has genetically separable functions in controlling bilaterally symmetric ASE neuron class specification and the ensuing left-right subtype specification program. Both neuron class specification and asymmetric subclass specification depend on CHE-1-binding sites (`ASE motifs') in symmetrically and asymmetrically expressed target genes, but in the case of asymmetrically expressed target genes, the activity of the ASE motif is modulated through a diverse set of additional cis-regulatory elements. Depending on the target gene, these cis-regulatory elements either promote or inhibit the activity of CHE-1. The activity of these L/R asymmetric cis-regulatory elements is indirectly controlled by che-1 itself, revealing a feed-forward loop configuration in which che-1 restricts its own activity. Relative binding affinity of CHE-1 to ASE motifs also depends on whether a gene is expressed bilaterally or in a left/right asymmetric manner. Our analysis provides insights into the molecular mechanisms of neuronal subtype specification, demonstrating that the activity of a neuron type-specific selector gene is modulated by a variety of distinct means to diversify individual neuron classes into specific subclasses. It also suggests that feed-forward loop motifs may be a prominent feature of neuronal diversification events.

Key words: C. elegans, Neuronal development, Left/right asymmetry, Transcriptional regulation

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

Related articles in Development:

A taste of neuronal specification

Development 2009 136: e13606. [Full Text]  

This article has been cited by other articles:

				J. Takayama, S. Faumont, H. Kunitomo, S. R. Lockery, and Y. Iino Single-cell transcriptional analysis of taste sensory neuron pair in Caenorhabditis elegans Nucleic Acids Res., October 29, 2009; (2009) gkp868v1. [Abstract] [Full Text] [PDF]

				S. Sarin, C. Antonio, B. Tursun, and O. Hobert The C. elegans Tailless/TLX transcription factor nhr-67 controls neuronal identity and left/right asymmetric fate diversification Development, September 1, 2009; 136(17): 2933 - 2944. [Abstract] [Full Text] [PDF]

				M. M. O'Meara, H. Bigelow, S. Flibotte, J. F. Etchberger, D. G. Moerman, and O. Hobert Cis-regulatory Mutations in the Caenorhabditis elegans Homeobox Gene Locus cog-1 Affect Neuronal Development Genetics, April 1, 2009; 181(4): 1679 - 1686. [Abstract] [Full Text] [PDF]

				K. T. Eade and D. W. Allan Neuronal Phenotype in the Mature Nervous System Is Maintained by Persistent Retrograde Bone Morphogenetic Protein Signaling J. Neurosci., March 25, 2009; 29(12): 3852 - 3864. [Abstract] [Full Text] [PDF]

				B. J. Lesch, A. R. Gehrke, M. L. Bulyk, and C. I. Bargmann Transcriptional regulation and stabilization of left-right neuronal identity in C. elegans Genes & Dev., February 1, 2009; 23(3): 345 - 358. [Abstract] [Full Text] [PDF]