The C. elegans POU-domain transcription factor UNC-86 regulates the tph-1 tryptophan hydroxylase gene and neurite outgrowth in specific serotonergic neurons

Development ◽  
2002 ◽  
Vol 129 (16) ◽  
pp. 3901-3911 ◽  
Author(s):  
Ji Ying Sze ◽  
Shenyuan Zhang ◽  
Jie Li ◽  
Gary Ruvkun
Keyword(s):  
Transcription Factor ◽  
Neurite Outgrowth ◽  
Serotonin Reuptake ◽  
Tryptophan Hydroxylase ◽  
Serotonin Synthesis ◽  
Serotonergic Neurons ◽  
C Elegans ◽  
Neuronal Types ◽  
Specific Regulation

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.

Goosecoid suppresses cell growth and enhances neuronal differentiation of PC12 cells

2000 ◽  
Vol 113 (15) ◽  
pp. 2705-2713
Author(s):  
K. Sawada ◽  
Y. Konishi ◽  
M. Tominaga ◽  
Y. Watanabe ◽  
J. Hirano ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Neurite Outgrowth ◽  
Neuronal Differentiation ◽  
Pc12 Cells ◽  
Mammalian Cells ◽  
Homeobox Gene ◽  
S Phase ◽  
Bhlh Transcription Factor ◽  
Spemann Organizer

In all vertebrate species, the homeobox gene goosecoid serves as a marker of the Spemann organizer tissue. One function of the organizer is the induction of neural tissue. To investigate the role of goosecoid in neuronal differentiation of mammalian cells, we have introduced goosecoid into PC12 cells. Expression of goosecoid resulted in reduced cell proliferation and enhanced neurite outgrowth in response to NGF. Expression of goosecoid led to a decrease in the percentage of S-phase cells and to upregulation of the expression of the neuron-specific markers MAP-1b and neurofilament-L. Analysis of goosecoid mutants revealed that these effects were independent of either DNA binding or homodimerization of Goosecoid. Coexpression of the N-terminal portion of the ets transcription factor PU.1, a protein that can bind to Goosecoid, repressed neurite outgrowth and rescued the proliferation of PC12 cultures. In contrast, expression of the bHLH transcription factor HES-1 repressed goosecoid-mediated neurite outgrowth without changing the proportion of S-phase cells. These results suggest that goosecoid is involved in neuronal differentiation in two ways, by slowing the cell cycle and stimulating neurite outgrowth, and that these two events are separately regulated.

scholarly journals The serotonin reuptake transporter is reduced in the epithelium of active Crohn’s disease and ulcerative colitis

2020 ◽  
Vol 319 (6) ◽  
pp. G761-G768
Author(s):  
Jonas Woll Jørandli ◽  
Silje Thorsvik ◽  
Helene Kolstad Skovdahl ◽  
Benedikt Kornfeld ◽  
Siri Sæterstad ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Crohn’S Disease ◽  
Intestinal Epithelium ◽  
Serotonin Reuptake ◽  
Tryptophan Hydroxylase ◽  
Intestinal Inflammation ◽  
Serotonin Synthesis ◽  
Crohn’S Colitis ◽  
Tnf Α ◽  
Serotonin Reuptake Transporter

The serotonin reuptake transporter is potently reduced in inflamed areas of Crohn’s ileitis, Crohn’s colitis, and ulcerative colitis. The changes are localized to the intestinal epithelium and can be induced by TNF-α. The serotonin synthesis through tryptophan hydroxylase 1 is unchanged. This regulation is suggested as a mechanism underlying the increased extracellular serotonin levels associated with intestinal inflammation.

scholarly journals Caenorhabditits elegans LRK-1 and PINK-1 Act Antagonistically in Stress Response and Neurite Outgrowth

2009 ◽  
Vol 284 (24) ◽  
pp. 16482-16491 ◽  
Author(s):  
Julia Sämann ◽  
Jan Hegermann ◽  
Erika von Gromoff ◽  
Stefan Eimer ◽  
Ralf Baumeister ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Stress Response ◽  
Parkinson Disease ◽  
Neurite Outgrowth ◽  
Physiological Role ◽  
Model Organisms ◽  
Loss Of Function ◽  
C Elegans ◽  
Genes Encoding

Mutations in two genes encoding the putative kinases LRRK2 and PINK1 have been associated with inherited variants of Parkinson disease. The physiological role of both proteins is not known at present, but studies in model organisms have linked their mutants to distinct aspects of mitochondrial dysfunction, increased vulnerability to oxidative and endoplasmic reticulum stress, and intracellular protein sorting. Here, we show that a mutation in the Caenorhabditits elegans homologue of the PTEN-induced kinase pink-1 gene resulted in reduced mitochondrial cristae length and increased paraquat sensitivity of the nematode. Moreover, the mutants also displayed defects in axonal outgrowth of a pair of canal-associated neurons. We demonstrate that in the absence of lrk-1, the C. elegans homologue of human LRRK2, all phenotypic aspects of pink-1 loss-of-function mutants were suppressed. Conversely, the hypersensitivity of lrk-1 mutant animals to the endoplasmic reticulum stressor tunicamycin was reduced in a pink-1 mutant background. These results provide the first evidence of an antagonistic role of PINK-1 and LRK-1. Due to the similarity of the C. elegans proteins to human LRRK2 and PINK1, we suggest a common role of both factors in cellular functions including stress response and regulation of neurite outgrowth. This study might help to link pink-1/PINK1 and lrk-1/LRRK2 function to the pathological processes resulting from Parkinson disease-related mutants in both genes, the first manifestations of which are cytoskeletal defects in affected neurons.

scholarly journals Examining the role of SUMOylation in C. elegans T-box transcription factor TBX-2 function

2011 ◽  
Vol 356 (1) ◽  
pp. 261
Author(s):  
Paul Huber ◽  
Tanya Crum ◽  
Peter Okkema
Keyword(s):  
Transcription Factor ◽  
T Box ◽  
C Elegans

scholarly journals TPH1 gene polymorphism rs211105 influences serotonin and tryptophan hydroxylase 1 concentrations in acute pancreatitis patients

2021 ◽  
Author(s):  
Jadwiga Snarska ◽  
Ewa Fiedorowicz ◽  
Dominika Rozmus ◽  
Konrad Wroński ◽  
Maria Latacz ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Metabolic Pathway ◽  
Tryptophan Hydroxylase ◽  
Control Group ◽  
Nucleotide Polymorphisms ◽  
Serotonin Synthesis ◽  
Single Nucleotide ◽  
Factors Affecting ◽  
Rate Limiting

Abstract Background The role of serotonin and its metabolic pathway in proper functioning of the pancreas has not been thoroughly investigated yet in acute pancreatitis (AP) patients. Tryptophan hydroxylase (TPH) as the rate-limiting enzyme of serotonin synthesis has been considered for possible associations in various diseases. Single-nucleotide polymorphisms (SNPs) in TPH genes have been already described in associations with psychiatric and digestive system disorders. This study aimed to explore the association of a rs211105 (T/G) polymorphism in TPH1 gene with tryptophan hydroxylase 1 concentrations in blood serum in a population of acute pancreatitis patients, and to investigate this association with acute pancreatitis susceptibility. Results Our data showed an association between the presence of the T allele at the position rs211105 (OR = 2.47, 95% CI: 0.94-6.50, p = 0.06) under conditions of a decreased AP incidence. For TT and GT genotypes in the control group, the lowest concentration of TPH was associated with higher serotonin levels (TT: Rs=-0.415, p=0.0018; GT: Rs=-0,457, p=0.0066), while for the AP group the highest levels of TPH among the TT genotype were associated with lower levels of serotonin (TT: Rs=-0.749, p<0.0001, and in the GG genotype higher levels of TPH were associated with higher levels of serotonin (GG: Rs=-0.738, p=0.037). Conclusions Here, a new insight in the potential role of a selected genetic factor in pancreatitis development was shown. Not only the metabolic pathway of serotonin, but also factors affecting serotonin synthesis may be interesting and important points in acute pancreatitis.

scholarly journals SNPC-1.3 is a sex-specific transcription factor that drives male piRNA expression in C. elegans

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Charlotte P Choi ◽  
Rebecca J Tay ◽  
Margaret R Starostik ◽  
Suhua Feng ◽  
James J Moresco ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Ectopic Expression ◽  
Sexually Dimorphic ◽  
Small Nuclear Rna ◽  
Germline Development ◽  
C Elegans ◽  
Male Germline ◽  
Nuclear Rna ◽  
Specific Regulation ◽  
Male Specific

Piwi-interacting RNAs (piRNAs) play essential roles in silencing repetitive elements to promote fertility in metazoans. Studies in worms, flies, and mammals reveal that piRNAs are expressed in a sex-specific manner. However, the mechanisms underlying this sex-specific regulation are unknown. Here we identify SNPC-1.3, a male germline-enriched variant of a conserved subunit of the small nuclear RNA-activating protein complex, as a male-specific piRNA transcription factor in Caenorhabditis elegans. SNPC-1.3 colocalizes with the core piRNA transcription factor, SNPC-4, in nuclear foci of the male germline. Binding of SNPC-1.3 at male piRNA loci drives spermatogenic piRNA transcription and requires SNPC-4. Loss of snpc-1.3 leads to depletion of male piRNAs and defects in male-dependent fertility. Furthermore, TRA-1, a master regulator of sex determination, binds to the snpc-1.3 promoter and represses its expression during oogenesis. Loss of TRA-1 targeting causes ectopic expression of snpc-1.3 and male piRNAs during oogenesis. Thus, sexually dimorphic regulation of snpc-1.3 expression coordinates male and female piRNA expression during germline development.

scholarly journals Expression Pattern, Regulation, and Biological Role of Runt Domain Transcription Factor, run, in Caenorhabditis elegans

2002 ◽  
Vol 22 (2) ◽  
pp. 547-554 ◽  
Author(s):  
Seunghee Nam ◽  
Yun-Hye Jin ◽  
Qing-Lin Li ◽  
Kwang-Youl Lee ◽  
Goo-Bo Jeong ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Caenorhabditis Elegans ◽  
Essential Role ◽  
Regulatory Elements ◽  
Intestinal Cells ◽  
Human Leukemia ◽  
Runt Domain ◽  
C Elegans ◽  
Intron Region

ABSTRACT The Caenorhabditis elegans run gene encodes a Runt domain factor. Runx1, Runx2, and Runx3 are the three known mammalian homologs of run. Runx1, which plays an essential role in hematopoiesis, has been identified at the breakpoint of chromosome translocations that are responsible for human leukemia. Runx2 plays an essential role in osteogenesis, and inactivation of one allele of Runx2 is responsible for the human disease cleidocranial dysplasia. To understand the role of run in C. elegans, we used transgenic run::GFP reporter constructs and a double-stranded RNA-mediated interference method. The expression of run was detected as early as the bean stage exclusively in the nuclei of seam hypodermal cells and lasted until the L3 stage. At the larval stage, expression of run was additionally detected in intestinal cells. The regulatory elements responsible for the postembryonic hypodermal seam cells and intestinal cells were separately located within a 7.2-kb-long intron region. This is the first report demonstrating that an intron region is essential for stage-specific and cell type-specific expression of a C. elegans gene. RNA interference analysis targeting the run gene resulted in an early larva-lethal phenotype, with apparent malformation of the hypodermis and intestine. These results suggest that run is involved in the development of a functional hypodermis and gut in C. elegans. The highly conserved role of the Runt domain transcription factor in gut development during evolution from nematodes to mammals is discussed.

scholarly journals Caenorhabditis eleganssensory neurons modulate pathogen specific responses via HLH-30/TFEB transcription factor and FSHR-1 GPCR axes of immunity

2019 ◽  
Author(s):  
Anjali Gupta ◽  
Manoj Varma ◽  
Varsha Singh
Keyword(s):  
Immune Response ◽  
Pattern Recognition ◽  
Transcription Factor ◽  
Sensory Perception ◽  
Immune Effector ◽  
C Elegans ◽  
Classical Pattern ◽  
Molecular Patterns ◽  
Ciliated Neurons

ABSTRACTPattern recognition receptors allow animals to sense microbe associated molecular patterns and mount effective immune responses. It is not clear howCaenorhabditis elegansrecognizes pathogenic microbes in absence of classical pattern recognition pathways. Here, we asked if sensory neurons ofC. elegansallow it to distinguish between pathogens. Exposure ofC. elegansto a Gram positive bacteriumEnterococcus faecalisor to a Gram negative bacteriumPseudomonas aeruginosashowed predominantly pathogen-specific signatures. Using nematodes defective in sensory perception, we show that neuronal sensing is essential to mount pathogen specific immune response. OSM-6 expressing, ciliated neurons exert non-cell autonomous control of immune effector production via an OSM-6-FSHR-1 GPCR axis as well as an OSM-6-HLH-30/TFEB transcription factor axis duringE. faecalisinfection. OSM-6-FSHR-1 axis also controls immune response toP. aeruginosa. In all, this study delineates essential role of sensory perception in the regulation of pathogen-specific immunity inC. elegans.

scholarly journals SNPC-1.3 is a sex-specific transcription factor that drives male piRNA expression in C. elegans

2020 ◽  
Author(s):  
Charlotte P. Choi ◽  
Rebecca J. Tay ◽  
Margaret R. Starostik ◽  
Suhua Feng ◽  
James J. Moresco ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Protein Complex ◽  
Ectopic Expression ◽  
Germline Development ◽  
Male And Female ◽  
C Elegans ◽  
The Core ◽  
Specific Manner ◽  
Specific Regulation ◽  
Male Specific

ABSTRACTPiwi-interacting RNAs (piRNAs) play essential roles in silencing repetitive elements to promote fertility in metazoans. Studies in worms, flies, and mammals reveal that piRNAs are expressed in a sex-specific manner. However, the mechanisms underlying this sex-specific regulation are unknown. Here we identify SNPC-1.3, a variant of a conserved subunit of the snRNA activating protein complex, as a male-specific piRNA transcription factor in C. elegans. Binding of SNPC-1.3 at male piRNA loci drives spermatogenic piRNA transcription and requires the core piRNA transcription factor SNPC-4. Loss of snpc-1.3 leads to depletion of male piRNAs and defects in male-dependent fertility. Furthermore, TRA-1, a master regulator of sex determination, binds to the snpc-1.3 promoter and represses its expression during oogenesis. Loss of TRA-1 targeting causes ectopic expression of snpc-1.3 and male piRNAs during oogenesis. Thus, sexual dimorphic regulation of snpc-1.3 coordinates male and female piRNA expression during germline development.

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