title: The LIM and POU homeobox genes ttx-3 and unc-86 act as terminal selectors in distinct cholinergic and serotonergic neuron types.
abstract: Transcription factors that drive neuron type-specific terminal differentiation programs in the developing nervous system are often expressed in several distinct neuronal cell types, but to what extent they have similar or distinct activities in individual neuronal cell types is generally not well explored. We investigate this problem using, as a starting point, the C. elegans LIM homeodomain transcription factor ttx-3, which acts as a terminal selector to drive the terminal differentiation program of the cholinergic AIY interneuron class. Using a panel of different terminal differentiation markers, including neurotransmitter synthesizing enzymes, neurotransmitter receptors and neuropeptides, we show that ttx-3 also controls the terminal differentiation program of two additional, distinct neuron types, namely the cholinergic AIA interneurons and the serotonergic NSM neurons. We show that the type of differentiation program that is controlled by ttx-3 in different neuron types is specified by a distinct set of collaborating transcription factors. One of the collaborating transcription factors is the POU homeobox gene unc-86, which collaborates with ttx-3 to determine the identity of the serotonergic NSM neurons. unc-86 in turn operates independently of ttx-3 in the anterior ganglion where it collaborates with the ARID-type transcription factor cfi-1 to determine the cholinergic identity of the IL2 sensory and URA motor neurons. In conclusion, transcription factors operate as terminal selectors in distinct combinations in different neuron types, defining neuron type-specific identity features.
authors.affiliation: Department of Biochemistry and Molecular Biophysics, Columbia University Medical Center, New York, NY 10032, USA.
authors.forename: Feifan
authors.initials: F
authors.lastname: Zhang
authors.forename: Abhishek
authors.initials: A
authors.lastname: Bhattacharya
authors.forename: Jessica C
authors.initials: JC
authors.lastname: Nelson
authors.forename: Namiko
authors.initials: N
authors.lastname: Abe
authors.forename: Patricia
authors.initials: P
authors.lastname: Gordon
authors.forename: Carla
authors.initials: C
authors.lastname: Lloret-Fernandez
authors.forename: Miren
authors.initials: M
authors.lastname: Maicas
authors.forename: Nuria
authors.initials: N
authors.lastname: Flames
authors.forename: Richard S
authors.initials: RS
authors.lastname: Mann
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Colón-Ramos
authors.forename: Oliver
authors.initials: O
authors.lastname: Hobert
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D059329:Cholinergic Neurons / Q000166:cytology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D017238:Genes, Helminth; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D007395:Interneurons / Q000166:cytology / Q000378:metabolism; D007814:Larva / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D055495:Neurogenesis / Q000235:genetics; D009474:Neurons / Q000145:classification / Q000166:cytology* / Q000378:metabolism*; D009479:Neuropeptides / Q000235:genetics* / Q000378:metabolism; D050809:POU Domain Factors / Q000235:genetics* / Q000378:metabolism; D059326:Serotonergic Neurons / Q000166:cytology / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: C454063:CFI-1 protein, C elegans; D029742:Caenorhabditis elegans Proteins; D018398:Homeodomain Proteins; D009479:Neuropeptides; D050809:POU Domain Factors; C108368:TTX-3 protein, C elegans; D014157:Transcription Factors; C081539:unc-86 protein, C elegans
keywords: Caenorhabditis elegans; Homeobox; Neuron differentiation