Regulation of C. Elegans Neuronal Differentiation by the ZEB-family Factor ZAG-1 and the NK-2 Homeodomain Factor CEH-28

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2014 Dec 5

PMID 25474681

Citations 8

Authors

Kalpana Ramakrishnan

Peter G Okkema

Affiliations

Soon will be listed here.

Abstract

The C. elegans pharyngeal neuron M4 is a multi-functional cell that acts as a cholinergic motor neuron to stimulate peristaltic pharyngeal muscle contraction and as a neuroendocrine cell secreting neuropeptides and growth factors to affect other cells both inside and outside the pharynx. The conserved transcription factors ZAG-1 and CEH-28 are co-expressed in M4 through most of development, and here we examine how these factors contribute to M4 differentiation. We find ZAG-1 functions upstream of CEH-28 in a branched pathway to activate expression of different sets of M4 differentiation markers. CEH-28 activates expression of the growth factor genes dbl-1 and egl-17, and the neuropeptide genes flp-5 and flp-2, while ZAG-1 activates expression of the serotonin receptor ser-7, as well as expression of ceh-28 and its downstream targets. Other markers of M4 differentiation are expressed normally in both zag-1 and ceh-28 mutants, including the neuropeptide gene flp-21 and the acetylcholine biosynthetic gene unc-17. Unlike ceh-28 mutants, zag-1 mutants completely lack peristaltic muscle contractions resulting from broader defects in M4 differentiation. Despite these defects, neither ZAG-1 nor CEH-28 are terminal selectors of the M4 phenotype, and we suggest they function in a hierarchy to regulate different aspects of M4 differentiation.

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References

Gerstein M, Lu Z, Van Nostrand E, Cheng C, Arshinoff B, Liu T . Integrative analysis of the Caenorhabditis elegans genome by the modENCODE project. Science. 2010; 330(6012):1775-87. PMC: 3142569. DOI: 10.1126/science.1196914. View

Wacker I, Schwarz V, Hedgecock E, Hutter H . zag-1, a Zn-finger homeodomain transcription factor controlling neuronal differentiation and axon outgrowth in C. elegans. Development. 2003; 130(16):3795-805. DOI: 10.1242/dev.00570. View

Franks C, Holden-Dye L, Bull K, Luedtke S, Walker R . Anatomy, physiology and pharmacology of Caenorhabditis elegans pharynx: a model to define gene function in a simple neural system. Invert Neurosci. 2006; 6(3):105-22. DOI: 10.1007/s10158-006-0023-1. View

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

Alfonso A, Grundahl K, Duerr J, Han H, Rand J . The Caenorhabditis elegans unc-17 gene: a putative vesicular acetylcholine transporter. Science. 1993; 261(5121):617-9. DOI: 10.1126/science.8342028. View

Song B, Avery L . Serotonin activates overall feeding by activating two separate neural pathways in Caenorhabditis elegans. J Neurosci. 2012; 32(6):1920-31. PMC: 3463504. DOI: 10.1523/JNEUROSCI.2064-11.2012. View

Albertson D, Thomson J . The pharynx of Caenorhabditis elegans. Philos Trans R Soc Lond B Biol Sci. 1976; 275(938):299-325. DOI: 10.1098/rstb.1976.0085. View

Vogler G, Urban J . The transcription factor Zfh1 is involved in the regulation of neuropeptide expression and growth of larval neuromuscular junctions in Drosophila melanogaster. Dev Biol. 2008; 319(1):78-85. DOI: 10.1016/j.ydbio.2008.04.008. View

Clark S, Chiu C . C. elegans ZAG-1, a Zn-finger-homeodomain protein, regulates axonal development and neuronal differentiation. Development. 2003; 130(16):3781-94. DOI: 10.1242/dev.00571. View

10.

Chen X, Chalfie M . Modulation of C. elegans touch sensitivity is integrated at multiple levels. J Neurosci. 2014; 34(19):6522-36. PMC: 4012311. DOI: 10.1523/JNEUROSCI.0022-14.2014. View

11.

Ringstad N, Horvitz H . FMRFamide neuropeptides and acetylcholine synergistically inhibit egg-laying by C. elegans. Nat Neurosci. 2008; 11(10):1168-76. PMC: 2963311. DOI: 10.1038/nn.2186. View

12.

Smith C, OBrien T, Chatzigeorgiou M, Spencer W, Feingold-Link E, Husson S . Sensory neuron fates are distinguished by a transcriptional switch that regulates dendrite branch stabilization. Neuron. 2013; 79(2):266-80. PMC: 3795438. DOI: 10.1016/j.neuron.2013.05.009. View

13.

Dillner N, Sanders M . Transcriptional activation by the zinc-finger homeodomain protein delta EF1 in estrogen signaling cascades. DNA Cell Biol. 2004; 23(1):25-34. DOI: 10.1089/104454904322745907. View

14.

Hirose T, Galvin B, Horvitz H . Six and Eya promote apoptosis through direct transcriptional activation of the proapoptotic BH3-only gene egl-1 in Caenorhabditis elegans. Proc Natl Acad Sci U S A. 2010; 107(35):15479-84. PMC: 2932601. DOI: 10.1073/pnas.1010023107. View

15.

Wakamatsu N, Yamada Y, Yamada K, Ono T, Nomura N, Taniguchi H . Mutations in SIP1, encoding Smad interacting protein-1, cause a form of Hirschsprung disease. Nat Genet. 2001; 27(4):369-70. DOI: 10.1038/86860. View

16.

Ramakrishnan K, Ray P, Okkema P . CEH-28 activates dbl-1 expression and TGF-β signaling in the C. elegans M4 neuron. Dev Biol. 2014; 390(2):149-59. PMC: 4023489. DOI: 10.1016/j.ydbio.2014.03.015. View

17.

Winner B, Marchetto M, Winkler J, Gage F . Human-induced pluripotent stem cells pave the road for a better understanding of motor neuron disease. Hum Mol Genet. 2014; 23(R1):R27-34. DOI: 10.1093/hmg/ddu205. View

18.

Burdine R, Branda C, Stern M . EGL-17(FGF) expression coordinates the attraction of the migrating sex myoblasts with vulval induction in C. elegans. Development. 1998; 125(6):1083-93. DOI: 10.1242/dev.125.6.1083. View

19.

Tomassy G, Lodato S, Arlotta P . A sip of GABA for the cerebral cortex. Neuron. 2013; 77(1):1-3. DOI: 10.1016/j.neuron.2012.12.026. View

20.

Ray P, Schnabel R, Okkema P . Behavioral and synaptic defects in C. elegans lacking the NK-2 homeobox gene ceh-28. Dev Neurobiol. 2007; 68(4):421-33. DOI: 10.1002/dneu.20599. View