Biomedical subjects

Kyuhyung Kim

Publications and source records attributed to Kyuhyung Kim.

4 recordsLinked to original sources

PubMed2005

The UNC-3 Olf/EBF protein represses alternate neuronal programs to specify chemosensory neuron identity.

Neuronal identities are specified by the combinatorial functions of activators and repressors of gene expression. Members of the well-conserved Olf/EBF (O/E) transcription factor family have been shown to play important roles in neuronal and non-neuronal development and differentiation. O/E proteins are highly expressed in the olfactory epithelium, and O/E binding sites have been identified upstream of olfactory genes. However, the roles of O/E proteins in sensory neuron development are unclear. Here we show that the O/E protein UNC-3 is required for subtype specification of the ASI chemosensory neurons in Caenorhabditis elegans. UNC-3 promotes an ASI identity by directly repressing the expression of alternate neuronal programs and by activating expression of ASI-specific genes including the daf-7 TGF-beta gene. Our results indicate that UNC-3 is a critical component of the transcription factor code that integrates cell-intrinsic developmental programs with external signals to specify sensory neuronal identity and suggest models for O/E protein functions in other systems.

Animals↗

PubMed2005

Convergent genetic programs regulate similarities and differences between related motor neuron classes in Caenorhabditis elegans.

How do genetic programs create features common to a specific cell or tissue type while generating modifications necessary for functional diversification? We have addressed this question using the nematode Caenorhabditis elegans. The dorsal D (DD) and ventral D (VD) motorneurons (mns), referred to collectively as the D mns, compose a cross-inhibitory network that contributes to the animal's sinuous locomotion. The D mns share a number of structural and functional features, but are distinguished from one another by their synaptic patterns and the expression of a neuropeptide gene. Our findings suggest that the similarities and differences are generated at the transcriptional level. UNC-30 contains a homeodomain and activates structural and functional genes expressed in both classes. UNC-55 is a nuclear receptor expressed in the VD mns that is necessary for generating features that distinguish the two classes of D mns from one another. In unc-55 mutants, the VD mns adopt the DD mn synaptic pattern and peptide expression profile. Conversely, ectopic expression of unc-55 in the DD mns causes them to adopt VD mn features. The promoter of the neuropeptide gene expressed in the DD mns contains putative binding sites for both UNC-30 and UNC-55; alteration of these sites suggests that UNC-55 represses the ability of UNC-30 to activate a subset of genes that are expressed in the DD mns but not in the VD mns. Thus UNC-55 acts as a switch for the features that distinguish these two functionally related classes of mns.

Amino Acid Motifs↗

PubMed2004

Expression and regulation of an FMRFamide-related neuropeptide gene family in Caenorhabditis elegans.

FMRFamide (Phe-Met-Arg-Phe-NH2) and related peptides (FaRPs) have been found throughout the animal kingdom, where they are involved in many behaviors. We previously identified 22 genes comprising the flp gene family that encodes FaRPs in Caenorhabditis elegans; in this paper we report the identification of another flp gene, flp-23. As a first step toward determining their functional roles in C. elegans, we examined the cell-specific expression pattern of the flp gene family. Of the 19 flp genes examined, each gene is expressed in a distinct set of cells; these cells include interneurons, motor neurons, and sensory neurons that are involved in multiple behaviors, as well as supporting cells, muscle cells, and epidermal cells. Several flp genes show sex-specific expression patterns. Furthermore, we find that expression of two flp genes changes in response to the developmental state of the animal. Many neurons express multiple flp genes. To investigate how flp genes are regulated in different neuronal subtypes, we examined flp expression in a small, well-defined subset of neurons, the mechanosensory neurons. Mutations in the unc-86 and mec-3 genes, which are necessary for the production and differentiation of the mechanosensory neurons, result in the complete loss of flp-4, flp-8, and flp-20 expression in mechanosensory neurons. Collectively, these data indicate that members of the flp gene family are likely to influence multiple behaviors and that their regulation can be dependent on the developmental state of the organism.

Animals↗

PubMed2003

Inhibition of Caenorhabditis elegans social feeding by FMRFamide-related peptide activation of NPR-1.

Social and solitary feeding in natural Caenorhabditis elegans isolates are associated with two alleles of the orphan G-protein-coupled receptor (GPCR) NPR-1: social feeders contain NPR-1 215F, whereas solitary feeders contain NPR-1 215V. Here we identify FMRFamide-related neuropeptides (FaRPs) encoded by the flp-18 and flp-21 genes as NPR-1 ligands and show that these peptides can differentially activate the NPR-1 215F and NPR-1 215V receptors. Multicopy overexpression of flp-21 transformed wild social animals into solitary feeders. Conversely, a flp-21 deletion partially phenocopied the npr-1(null) phenotype, which is consistent with NPR-1 activation by FLP-21 in vivo but also implicates other ligands for NPR-1. Phylogenetic studies indicate that the dominant npr-1 215V allele likely arose from an ancestral npr-1 215F gene in C. elegans. Our data suggest a model in which solitary feeding evolved in an ancestral social strain of C. elegans by a gain-of-function mutation that modified the response of NPR-1 to FLP-18 and FLP-21 ligands.

Action Potentials↗