title: Regulation of C. elegans neuronal differentiation by the ZEB-family factor ZAG-1 and the NK-2 homeodomain factor CEH-28.
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.
authors.affiliation: Department of Biological Sciences, University of Illinois at Chicago, Chicago, Illinois, United States of America.
authors.forename: Kalpana
authors.initials: K
authors.lastname: Ramakrishnan
authors.affiliation: Department of Biological Sciences, University of Illinois at Chicago, Chicago, Illinois, United States of America.
authors.forename: Peter G
authors.initials: PG
authors.lastname: Okkema
mesh_terms: D000818:Animals; D001115:Arecoline / Q000494:pharmacology; D017173:Caenorhabditis elegans / Q000166:cytology* / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D005247:Feeding Behavior / Q000187:drug effects; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D007814:Larva / Q000187:drug effects / Q000378:metabolism; D009154:Mutation; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism; D010528:Peristalsis / Q000187:drug effects; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D012701:Serotonin / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D014157:Transcription Factors / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D050494:Vesicular Acetylcholine Transport Proteins / Q000378:metabolism
chemical_list: C000588937:CEH-28 protein, C elegans; D029742:Caenorhabditis elegans Proteins; C117509:Dbl-1 protein, C elegans; C105157:Egl-17 protein, C elegans; D018398:Homeodomain Proteins; D036341:Intercellular Signaling Peptides and Proteins; D009479:Neuropeptides; D012097:Repressor Proteins; D017366:Serotonin Receptor Agonists; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; C082365:Unc-17 protein, C elegans; D050494:Vesicular Acetylcholine Transport Proteins; C477509:ZAG-1 protein, C elegans; D012701:Serotonin; D001115:Arecoline