Van Buskirk, Cheryl and Sternberg, Paul W. (2010) Paired and LIM class homeodomain proteins coordinate differentiation of the C. elegans ALA neuron. Development, 137 (12). pp. 2065-2074. ISSN 0950-1991 http://resolver.caltech.edu/CaltechAUTHORS:20100615-133523696
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The ancient origin of sleep is evidenced by deeply conserved signaling pathways regulating sleep-like behavior, such as signaling through the Epidermal growth factor receptor (EGFR). In Caenorhabditis elegans, a sleep-like state can be induced at any time during development or adulthood through conditional expression of LIN-3/EGF. The behavioral response to EGF is mediated by EGFR activity within a single cell, the ALA neuron, and mutations that impair ALA differentiation are expected to confer EGF-resistance. Here we describe three such EGF-resistant mutants. One of these corresponds to the LIM class homeodomain (HD) protein CEH-14/Lhx3, and the other two correspond to Paired-like HD proteins CEH-10/Chx10 and CEH-17/Phox2. Whereas CEH-14 is required for ALA-specific gene expression throughout development, the Prd-like proteins display complementary temporal contributions to gene expression, with the requirement for CEH-10 decreasing as that of CEH-17 increases. We present evidence that CEH-17 participates in a positive autoregulatory loop with CEH-14 in ALA, and that CEH-10, in addition to its role in ALA differentiation, functions in the generation of the ALA neuron. Similarly to CEH-17, CEH-10 is required for the posterior migration of the ALA axons, but CEH-14 appears to regulate an aspect of ALA axon outgrowth that is distinct from that of the Prd-like proteins. Our findings reveal partial modularity among the features of a neuronal differentiation program and their coordination by Prd and LIM class HD proteins.
|Additional Information:||© 2010 Published by The Company of Biologists Ltd. Accepted April 20, 2010. We are grateful to N. Pujol for reporter constructs and insightful comments and to H. Kagoshima and T. Bürglin for sharing unpublished observations. We thank M. Nonet, M. Treinin, S. Xu, G. Schindelman, R. Roubin, I. Hope, C. Li and T. Cai for reporter constructs, the Caenorhabditis Genetics Center for strains, members of the Sternberg lab for helpful discussions and O. Hobert and A. Wright for critical reading of the manuscript. This work was supported by a grant from the US National Institute on Drug Abuse (DA018341) to P.W.S., an investigator of the HHMI. Deposited in PMC for release after 6 months.|
|Subject Keywords:||EGFR; Axon migration; Gene battery; Homeodomain; Sleep; C. elegans|
|Official Citation:||Van Buskirk, C. and P. W. Sternberg (2010). "Paired and LIM class homeodomain proteins coordinate differentiation of the C. elegans ALA neuron." Development 137(12): 2065-2074; doi:10.1242/dev.040881|
|Usage Policy:||No commercial reproduction, distribution, display or performance rights in this work are provided.|
|Deposited By:||Tony Diaz|
|Deposited On:||15 Jul 2010 23:38|
|Last Modified:||26 Dec 2012 12:08|
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