The C. elegans POU-domain transcription factor UNC-86 regulates the tph-1 tryptophan hydroxylase gene and neurite outgrowth in specific serotonergic neurons.
A fundamental question in developmental neurobiology is how a common neurotransmitter is specified in different neuronal types?. We describe cell-specific regulation of the serotonergic phenotype by the C. elegans POU-transcription factor UNC-86. We show that unc-86 regulates particular aspects of the terminal neuronal identity in four classes of serotonergic neurons, but that the development of the ADF serotonergic neurons is regulated by an UNC-86-independent program. In the NSM neurons, the role of unc-86 is confined in late differentiation; the neurons are generated but do not express genes necessary for serotonergic neurotransmission. unc-86-null mutations affect the expression in NSM of tph-1, which encodes the serotonin synthetic enzyme tryptophan hydroxylase, and cat-1, which encodes a vesicular transporter that loads serotonin into synaptic vesicles, suggesting that unc-86 coordinately regulates serotonin synthesis and packaging. However, unc-86-null mutations do not impair the ability of NSM to reuptake serotonin released from the ADF serotonergic chemosensory neurons and this serotonin reuptake is sensitive to the serotonin reuptake block drugs imipramine and fluoxetine, demonstrating that serotonin synthesis and reuptake is regulated by distinct factors. The NSM neurons in unc-86-null mutants also display abnormal neurite outgrowth, suggesting a role of unc-86 in regulating this process as well.
Department of Anatomy and Neurobiology, College of Medicine, University of California, Irvine, Irvine, CA 92697, USA. jsze@uci.edu
Ji Ying
JY
Sze
Shenyuan
S
Zhang
Jie
J
Li
Gary
G
Ruvkun
D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics; D002470:Cell Survival; D018507:Gene Expression Regulation, Developmental; D017238:Genes, Helminth; D005801:Genes, Homeobox; D018398:Homeodomain Proteins / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000235:genetics; D026901:Membrane Transport Proteins; D009154:Mutation; D009419:Nerve Tissue Proteins; D016501:Neurites / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D050809:POU Domain Factors; D010641:Phenotype; D012701:Serotonin / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins; D014157:Transcription Factors / Q000378:metabolism*; D014365:Tryptophan Hydroxylase / Q000235:genetics*
D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D018398:Homeodomain Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D050809:POU Domain Factors; D050486:Serotonin Plasma Membrane Transport Proteins; D014157:Transcription Factors; C493229:mod-5 protein, C elegans; C081539:unc-86 protein, C elegans; D012701:Serotonin; D014365:Tryptophan Hydroxylase