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Notch-dependent induction of left/right asymmetry in C. elegans interneurons and motoneurons.

Bertrand, V; Bisso, P; Poole, RJ; Hobert, O; (2011) Notch-dependent induction of left/right asymmetry in C. elegans interneurons and motoneurons. Curr Biol , 21 (14) pp. 1225-1231. 10.1016/j.cub.2011.06.016.

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Abstract

Although nervous systems are largely bilaterally symmetric on a structural level, they display striking degrees of functional left/right (L/R) asymmetry. In Caenorhabditis elegans, two structurally symmetric pairs of sensory neurons, ASE and AWC, display two distinctly controlled types of functional L/R asymmetries (stereotyped versus stochastic asymmetry). Beyond these two cases, the extent of neuronal asymmetry in the C. elegans nervous system was unclear. Here, we report that the Beta3/Olig-type bHLH transcription factor hlh-16 is L/R asymmetrically expressed in several distinct, otherwise bilaterally symmetric interneuron and motoneuron pairs that are part of a known navigation circuit. We find that hlh-16 asymmetry is generated during gastrulation by an asymmetric LAG-2/Delta signal originating from the mesoderm that promotes hlh-16 expression in neurons on the left side through direct binding of the Notch effector LAG-1/Su(H)/CBF to a cis-regulatory element in the hlh-16 locus. Removal of hlh-16 reveals an unanticipated asymmetry in the ability of the axons of the AIY interneurons to extend into the nerve ring, with the left AIY axon requiring elevated hlh-16 expression for correct extension. Our study suggests that the extent of molecular L/R asymmetry in the C. elegans nervous system is broader than previously anticipated, establishes a novel signaling mechanism that crosses germ layers to diversify bilaterally symmetric neuronal lineages, and reveals L/R asymmetric control of axonal outgrowth of bilaterally symmetric neurons.

Type: Article
Title: Notch-dependent induction of left/right asymmetry in C. elegans interneurons and motoneurons.
Location: England
DOI: 10.1016/j.cub.2011.06.016
Keywords: Animals, Basic Helix-Loop-Helix Transcription Factors, Body Patterning, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Gene Expression Regulation, Developmental, Interneurons, Membrane Glycoproteins, Motor Neurons
UCL classification: UCL > School of Life and Medical Sciences
UCL > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > School of Life and Medical Sciences > Faculty of Life Sciences > Biosciences (Division of) > Cell and Developmental Biology
URI: http://discovery.ucl.ac.uk/id/eprint/1369016
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