Transcriptional Regulation and Stabilization of Left-right Neuronal Identity in C. Elegans

Overview

Journal Genes Dev

Specialty Molecular Biology

Date 2009 Feb 11

PMID 19204119

Citations 36

Authors

Bluma J Lesch

Andrew R Gehrke

Martha L Bulyk

Cornelia I Bargmann

Affiliations

Soon will be listed here.

Abstract

At discrete points in development, transient signals are transformed into long-lasting cell fates. For example, the asymmetric identities of two Caenorhabditis elegans olfactory neurons called AWC(ON) and AWC(OFF) are specified by an embryonic signaling pathway, but maintained throughout the life of an animal. Here we show that the DNA-binding protein NSY-7 acts to convert a transient, partially differentiated state into a stable AWC(ON) identity. Expression of an AWC(ON) marker is initiated in nsy-7 loss-of-function mutants, but subsequently lost, so that most adult animals have two AWC(OFF) neurons and no AWC(ON) neurons. nsy-7 encodes a protein with distant similarity to a homeodomain. It is expressed in AWC(ON), and is an early transcriptional target of the embryonic signaling pathway that specifies AWC(ON) and AWC(OFF); its expression anticipates future AWC asymmetry. The NSY-7 protein binds a specific optimal DNA sequence that was identified through a complete biochemical survey of 8-mer DNA sequences. This sequence is present in the promoter of an AWC(OFF) marker and essential for its asymmetric expression. An 11-base-pair (bp) sequence required for AWC(OFF) expression has two activities: One region activates expression in both AWCs, and the overlapping NSY-7-binding site inhibits expression in AWC(ON). Our results suggest that NSY-7 responds to transient embryonic signaling by repressing AWC(OFF) genes in AWC(ON), thus acting as a transcriptional selector for a randomly specified neuronal identity.

Citing Articles

The AWC neuron is important for attraction to 1-butanol in .

Brown V, Bradley E, Asaed T, Lo S, Bellini Z, Blackett D MicroPubl Biol. 2025; 2025.

PMID: 39882098 PMC: 11775657. DOI: 10.17912/micropub.biology.001370.

Synergistic roles of homeodomain proteins UNC-62 homothorax and MLS-2 HMX/NKX in the specification of olfactory neurons in Caenorhabditis elegans.

Hsieh Y, Xiong R, Chuang C Genetics. 2021; 219(2).

PMID: 34849889 PMC: 8633082. DOI: 10.1093/genetics/iyab133.

Molecular topography of an entire nervous system.

Taylor S, Santpere G, Weinreb A, Barrett A, Reilly M, Xu C Cell. 2021; 184(16):4329-4347.e23.

PMID: 34237253 PMC: 8710130. DOI: 10.1016/j.cell.2021.06.023.

Spaceflight affects neuronal morphology and alters transcellular degradation of neuronal debris in adult .

Laranjeiro R, Harinath G, Pollard A, Gaffney C, Deane C, Vanapalli S iScience. 2021; 24(2):102105.

PMID: 33659873 PMC: 7890410. DOI: 10.1016/j.isci.2021.102105.

Fusogen-mediated neuron-neuron fusion disrupts neural circuit connectivity and alters animal behavior.

Giordano-Santini R, Kaulich E, Galbraith K, Ritchie F, Wang W, Li Z Proc Natl Acad Sci U S A. 2020; 117(37):23054-23065.

PMID: 32855296 PMC: 7502713. DOI: 10.1073/pnas.1919063117.

References

Rushlow C, Colosimo P, Lin M, Xu M, Kirov N . Transcriptional regulation of the Drosophila gene zen by competing Smad and Brinker inputs. Genes Dev. 2001; 15(3):340-51. PMC: 312624. DOI: 10.1101/gad.861401. View

Wigle J, Eisenstat D . Homeobox genes in vertebrate forebrain development and disease. Clin Genet. 2008; 73(3):212-26. DOI: 10.1111/j.1399-0004.2008.00967.x. View

Lanjuin A, VanHoven M, Bargmann C, Thompson J, Sengupta P . Otx/otd homeobox genes specify distinct sensory neuron identities in C. elegans. Dev Cell. 2003; 5(4):621-33. DOI: 10.1016/s1534-5807(03)00293-4. View

Brenner S . The genetics of Caenorhabditis elegans. Genetics. 1974; 77(1):71-94. PMC: 1213120. DOI: 10.1093/genetics/77.1.71. View

Wes P, Bargmann C . C. elegans odour discrimination requires asymmetric diversity in olfactory neurons. Nature. 2001; 410(6829):698-701. DOI: 10.1038/35070581. View

Chen R, Akbarian S, TUDOR M, Jaenisch R . Deficiency of methyl-CpG binding protein-2 in CNS neurons results in a Rett-like phenotype in mice. Nat Genet. 2001; 27(3):327-31. DOI: 10.1038/85906. View

Chuang C, Bargmann C . A Toll-interleukin 1 repeat protein at the synapse specifies asymmetric odorant receptor expression via ASK1 MAPKKK signaling. Genes Dev. 2004; 19(2):270-81. PMC: 545892. DOI: 10.1101/gad.1276505. View

Sieburth D, Chng Q, Dybbs M, Tavazoie M, Kennedy S, Wang D . Systematic analysis of genes required for synapse structure and function. Nature. 2005; 436(7050):510-7. DOI: 10.1038/nature03809. View

Sulston J, Horvitz H . Post-embryonic cell lineages of the nematode, Caenorhabditis elegans. Dev Biol. 1977; 56(1):110-56. DOI: 10.1016/0012-1606(77)90158-0. View

10.

Berger M, Philippakis A, Qureshi A, He F, Estep 3rd P, Bulyk M . Compact, universal DNA microarrays to comprehensively determine transcription-factor binding site specificities. Nat Biotechnol. 2006; 24(11):1429-35. PMC: 4419707. DOI: 10.1038/nbt1246. View

11.

Daniels S, Ailion M, Thomas J, SENGUPTA P . egl-4 acts through a transforming growth factor-beta/SMAD pathway in Caenorhabditis elegans to regulate multiple neuronal circuits in response to sensory cues. Genetics. 2000; 156(1):123-41. PMC: 1461244. DOI: 10.1093/genetics/156.1.123. View

12.

Chuang C, VanHoven M, Fetter R, Verselis V, Bargmann C . An innexin-dependent cell network establishes left-right neuronal asymmetry in C. elegans. Cell. 2007; 129(4):787-99. DOI: 10.1016/j.cell.2007.02.052. View

13.

Chi Y . Homeodomain revisited: a lesson from disease-causing mutations. Hum Genet. 2005; 116(6):433-44. PMC: 1579204. DOI: 10.1007/s00439-004-1252-1. View

14.

LEtoile N, Bargmann C . Olfaction and odor discrimination are mediated by the C. elegans guanylyl cyclase ODR-1. Neuron. 2000; 25(3):575-86. DOI: 10.1016/s0896-6273(00)81061-2. View

15.

Newburger D, Bulyk M . UniPROBE: an online database of protein binding microarray data on protein-DNA interactions. Nucleic Acids Res. 2008; 37(Database issue):D77-82. PMC: 2686578. DOI: 10.1093/nar/gkn660. View

16.

Berger M, Bulyk M . Universal protein-binding microarrays for the comprehensive characterization of the DNA-binding specificities of transcription factors. Nat Protoc. 2009; 4(3):393-411. PMC: 2908410. DOI: 10.1038/nprot.2008.195. View

17.

Sagasti A, HISAMOTO N, Hyodo J, Matsumoto K, Bargmann C . The CaMKII UNC-43 activates the MAPKKK NSY-1 to execute a lateral signaling decision required for asymmetric olfactory neuron fates. Cell. 2001; 105(2):221-32. DOI: 10.1016/s0092-8674(01)00313-0. View

18.

Koga M, Ohshima Y . The C. elegans ceh-36 gene encodes a putative homemodomain transcription factor involved in chemosensory functions of ASE and AWC neurons. J Mol Biol. 2004; 336(3):579-87. DOI: 10.1016/j.jmb.2003.12.037. View

19.

Lans H, Jansen G . Noncell- and cell-autonomous G-protein-signaling converges with Ca2+/mitogen-activated protein kinase signaling to regulate str-2 receptor gene expression in Caenorhabditis elegans. Genetics. 2006; 173(3):1287-99. PMC: 1526693. DOI: 10.1534/genetics.106.058750. View

20.

Tsunozaki M, Chalasani S, Bargmann C . A behavioral switch: cGMP and PKC signaling in olfactory neurons reverses odor preference in C. elegans. Neuron. 2008; 59(6):959-71. PMC: 2586605. DOI: 10.1016/j.neuron.2008.07.038. View