A predicted membrane protein, TRA-2A, directs hermaphrodite development in Caenorhabditis elegans

Development ◽  
1995 ◽  
Vol 121 (9) ◽  
pp. 2995-3004 ◽  
Author(s):  
P.E. Kuwabara ◽  
J. Kimble
Keyword(s):  
Heat Shock ◽  
Membrane Protein ◽  
Cell Fate ◽  
Loss Of Function ◽  
Heat Shock Promoter ◽  
Somatic Development ◽  
C Elegans ◽  
Cellular Domain ◽  
Carboxy Terminal ◽  
Necessary And Sufficient

The nematode C. elegans naturally develops as either an XO male or XX hermaphrodite. The sex-determining gene, tra-2, promotes hermaphrodite development in XX animals. This gene encodes a predicted membrane protein, named TRA-2A, which has been proposed to provide the primary feminising activity of the tra-2 locus. Here, we show that transgenic TRA-2A driven from a heat shock promoter can fully feminise the somatic tissues of XX tra-2 loss-of-function mutants, which would otherwise develop as male. TRA-2A is thus likely to provide a component of the tra-2 locus that is both necessary and sufficient to promote female somatic development. Transgenic TRA-2A driven by the heat shock promoter can also transform XO animals from male to self-fertile hermaphrodite. This result establishes the role of tra-2 as a developmental switch that controls somatic sexual cell fate. We show that a carboxy-terminal region of TRA-2A, predicted to be intra-cellular, can partially feminise XX tra-2 loss-of-function mutants and XO tra-2(+) males. We suggest that this intra-cellular domain of TRA-2A promotes hermaphrodite development by negatively regulating the FEM proteins.

scholarly journals tra-2 encodes a membrane protein and may mediate cell communication in the Caenorhabditis elegans sex determination pathway.

1992 ◽  
Vol 3 (4) ◽  
pp. 461-473 ◽  
Author(s):  
P E Kuwabara ◽  
P G Okkema ◽  
J Kimble
Keyword(s):  
Caenorhabditis Elegans ◽  
Membrane Protein ◽  
Sex Determination ◽  
Cell Fate ◽  
Cell Communication ◽  
Direct Repeat ◽  
Loss Of Function ◽  
Terminal Domain ◽  
Carboxy Terminal Domain ◽  
Carboxy Terminal

The Caenorhabditis elegans sex-determining gene, tra-2, promotes female development in XX animals. In this paper we report the cDNA sequence corresponding to a 4.7 kb tra-2 mRNA and show that it is composed of 23 exons, is trans-spliced to SL2, and contains a perfect direct repeat in the 3' untranslated region. This mRNA is predicted to encode a 1475 amino acid protein, named pTra2A, that has a secretory signal and several potential membrane-spanning domains. The molecular analysis of tra-2 loss-of-function mutations supports our open reading frame identification and suggests that the carboxy-terminal domain is important for tra-2 activity. We propose that in XX animals the carboxy-terminal domain of pTra2A negatively regulates the downstream male promoting fem genes. In XO animals, tra-2 is negatively regulated by her-1, which acts cell nonautonomously. Because hydropathy predictions suggest that pTra2A is an integral membrane protein, pTra2A might act as a receptor for the her-1 protein. We propose that in XO animals, the her-1 protein promotes male development by binding and inactivating pTra2A. The role of cell communication in C. elegans sex determination might be to ensure unified sexual development throughout the animal. If so, then regulation of sexual fate by her-1 and tra-2 might provide a general model for the coordination of groups of cells to follow a single cell fate.

scholarly journals Enhancers of glp-1, a gene required for cell-signaling in Caenorhabditis elegans, define a set of genes required for germline development.

Genetics ◽  
1995 ◽  
Vol 141 (2) ◽  
pp. 551-569 ◽  
Author(s):  
L Qiao ◽  
J L Lissemore ◽  
P Shu ◽  
A Smardon ◽  
M B Gelber ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Cell Signaling ◽  
Cell Fate ◽  
Gene Families ◽  
Loss Of Function ◽  
Germline Development ◽  
Somatic Development ◽  
C Elegans ◽  
Functional Relationships ◽  
New Genes

Abstract The distal tip cell (DTC) regulates the proliferation or differentiation choice in the Caenorhabditis elegans germline by an inductive mechanism. Cell signaling requires a putative receptor in the germline, encoded b y the glp-1 gene, and a putative signal from the DTC, encoded by the lag-2 gene. Both glp-1 and lag-2 belong to multigene gene families whose members are essential for cell signaling during development of various tissues in insects and vertebrates as well as C. elegans. Relatively little is known about how these pathways regulate cell fate choice. To identify additional genes involved in the glp-1 signaling pathway, we carried out screens for genetic enhancers of glp-1. We recovered mutations in five new genes, named ego (enhancer of glp-1), and two previously identified genes, lag-1 and glp-4, that strongly enhance a weak glp-1 loss-of-function phenotype in the germline. Ego mutations cause multiple phenotypes consistent with the idea that gene activity is required for more than one aspect of germline and, in some cases, somatic development. Based on genetic experiments, glp-1 appears to act upstream of ego-1 and ego-3. We discuss the possible functional relationships among these genes in light of their phenotypes and interactions with glp-1.

scholarly journals Rescue of a developmental arrest caused by a C. elegans heat-shock transcription-factor mutation by loss of ribosomal S6-kinase activity

2018 ◽  
Author(s):  
Peter Chisnell ◽  
T. Richard Parenteau ◽  
Elizabeth Tank ◽  
Kaveh Ashrafi ◽  
Cynthia Kenyon
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Heat Shock ◽  
Heat Shock Transcription Factor ◽  
Adult Longevity ◽  
Loss Of Function ◽  
S6 Kinase ◽  
Heat Shock Transcription Factors ◽  
C Elegans ◽  
Developmental Arrest

AbstractThe widely conserved heat-shock response, regulated by heat shock transcription factors, is not only essential for cellular stress resistance and adult longevity, but also for proper development. However, the genetic mechanisms by which heat-shock transcription factors regulate development are not well understood. In C. elegans, we conducted an unbiased genetic screen to identify mutations that could ameliorate the developmental arrest phenotype of a heat-shock factor mutant. Here we show that loss of the conserved translational activator rsks-1/S6-Kinase, a downstream effector of TOR kinase, can rescue the developmental-arrest phenotype of hsf-1 partial loss-of-function mutants. Unexpectedly, we show that the rescue is not likely caused by reduced translation, nor to activation of any of a variety of stress-protective genes and pathways. Our findings identify an as-yet unexplained regulatory relationship between the heat-shock transcription factor and the TOR pathway during C. elegans’ development.

scholarly journals A cohort of Caenorhabditis species lacking the highly conserved let-7 microRNA

2020 ◽  
Author(s):  
Charles Nelson ◽  
Victor Ambros
Keyword(s):  
Cell Fate ◽  
Nematode Species ◽  
Loss Of Function ◽  
Animal Development ◽  
C Elegans ◽  
Adult Transition ◽  
Developmental Progression ◽  
Caenorhabditis Species ◽  
Heterochronic Gene ◽  
Bilaterian Animal

ABSTRACTlet-7 is a highly conserved microRNA with critical functions integral to cell fate specification and developmental progression in diverse animals. In Caenorhabditis elegans, let-7 is a component of the heterochronic (developmental timing) gene regulatory network, and loss-of-function mutations of let-7 result in lethality during the larval to adult transition due to misregulation of the conserved let-7 target, lin-41. To date, no bilaterian animal lacking let-7 has been characterized. In this study, we identify a cohort of nematode species within the genus Caenorhabditis, closely related to C. elegans, that lack the let-7 microRNA, owing to absence of the let-7 gene. Using C. sulstoni as a representative let-7-lacking species to characterize normal larval development in the absence of let-7, we demonstrate that, except for the lack of let-7, the heterochronic gene network is otherwise functionally conserved. We also report that species lacking let-7 contain a group of divergent let-7 orthologs -- also known as the let-7-family of microRNAs -- that have apparently assumed the role of targeting the lin-41 mRNA.Summary StatementWe have identified a group of Caenorhabditis species that lack let-7a, an otherwise highly conserved and nearly ubiquitous microRNA that was previously thought to be critical to bilaterian animal development.

scholarly journals A cohort of Caenorhabditis species lacking the highly conserved let-7 microRNA

2021 ◽  
Author(s):  
Charles Nelson ◽  
Victor Ambros
Keyword(s):  
Cell Fate ◽  
Nematode Species ◽  
Loss Of Function ◽  
C Elegans ◽  
Adult Transition ◽  
Developmental Progression ◽  
Caenorhabditis Species ◽  
Heterochronic Gene ◽  
Bilaterian Animal

Abstract The let-7 gene encodes a highly conserved microRNA with critical functions integral to cell fate specification and developmental progression in diverse animals. In Caenorhabditis elegans, let-7 is a component of the heterochronic (developmental timing) gene regulatory network, and loss-of-function mutations of let-7 result in lethality during the larval to adult transition due to misregulation of the conserved let-7 target, lin-41. To date, no bilaterian animal lacking let-7 has been characterized. In this study, we identify a cohort of nematode species within the genus Caenorhabditis, closely related to C. elegans, that lack the let-7 microRNA, owing to absence of the let-7 gene. Using C. sulstoni as a representative let-7-lacking species to characterize normal larval development in the absence of let-7, we demonstrate that, except for the lack of let-7, the heterochronic gene network is otherwise functionally conserved. We also report that species lacking let-7 contain a group of divergent let-7 paralogs—also known as the let-7-family of microRNAs—that have apparently assumed the role of targeting the lin-41 mRNA.

Patterning of dopaminergic neurotransmitter identity among Caenorhabditis elegans ray sensory neurons by a TGFbeta family signaling pathway and a Hox gene

Development ◽  
1999 ◽  
Vol 126 (24) ◽  
pp. 5819-5831 ◽  
Author(s):  
R. Lints ◽  
S.W. Emmons
Keyword(s):  
Caenorhabditis Elegans ◽  
Heat Shock ◽  
Signaling Pathway ◽  
Cell Fate ◽  
Sensory Neurons ◽  
Ectopic Expression ◽  
Temperature Shift ◽  
Temperature Sensitive ◽  
Loss Of Function ◽  
Hox Gene

We have investigated the mechanism that patterns dopamine expression among Caenorhabditis elegans male ray sensory neurons. Dopamine is expressed by the A-type sensory neurons in three out of the nine pairs of rays. We used expression of a tyrosine hydroxylase reporter transgene as well as direct assays for dopamine to study the genetic requirements for adoption of the dopaminergic cell fate. In loss-of-function mutants affecting a TGFbeta family signaling pathway, the DBL-1 pathway, dopaminergic identity is adopted irregularly by a wider subset of the rays. Ectopic expression of the pathway ligand, DBL-1, from a heat-shock-driven transgene results in adoption of dopaminergic identity by rays 3–9; rays 1 and 2 are refractory. The rays are therefore prepatterned with respect to their competence to be induced by a DBL-1 pathway signal. Temperature-shift experiments with a temperature-sensitive type II receptor mutant, as well as heat-shock induction experiments, show that the DBL-1 pathway acts during an interval that extends from two to one cell generation before ray neurons are born and begin to differentiate. In a mutant of the AbdominalB class Hox gene egl-5, rays that normally express EGL-5 do not adopt dopaminergic fate and cannot be induced to express DA when DBL-1 is provided by a heat-shock-driven dbl-1 transgene. Therefore, egl-5 is required for making a subset of rays capable of adopting dopaminergic identity, while the function of the DBL-1 pathway signal is to pattern the realization of this capability.

The expression of TGFβ signal transducers in the hypodermis regulates body size inC. elegans

Development ◽  
2002 ◽  
Vol 129 (21) ◽  
pp. 4989-4998 ◽  
Author(s):  
Jianjun Wang ◽  
Rafal Tokarz ◽  
Cathy Savage-Dunn
Keyword(s):  
Nervous System ◽  
Body Size ◽  
Protein Accumulation ◽  
Type I ◽  
Loss Of Function ◽  
Signal Transducers ◽  
C Elegans ◽  
Genetic Mosaic ◽  
Mosaic Analysis ◽  
Necessary And Sufficient

In C. elegans, a TGFβ-related signaling pathway regulates body size. Loss of function of the signaling ligand (dbl-1),receptors (daf-4 and sma-6) or Smads (sma-2, sma-3and sma-4) results in viable, but smaller animals because of a reduction in postembryonic growth. We have investigated the tissue specificity of this pathway in body size regulation. We show that different tissues are reduced in size by different proportions, with hypodermal blast cell size most closely proportional to body size. We show that SMA-3 Smad is expressed in pharynx, intestine and hypodermis, as has been previously reported for the type I receptor SMA-6. Furthermore, we find that SMA-3::GFP is nuclear localized in all of these tissues, and that nuclear localization is enhanced by SMA-6 activity. Interestingly, SMA-3 protein accumulation was found to be negatively regulated by the level of Sma/Mab pathway activity. Using genetic mosaic analysis and directed expression of SMA-3, we find that SMA-3 activity in the hypodermis is necessary and sufficient for normal body size. Asdbl-1 is expressed primarily in the nervous system, these results suggest a model in which postembryonic growth of hypodermal cells is regulated by TGFβ-related signaling from the nervous system to the hypodermis.

The maternal par genes and the segregation of cell fate specification activities in early Caenorhabditis elegans embryos

Development ◽  
1997 ◽  
Vol 124 (19) ◽  
pp. 3815-3826 ◽  
Author(s):  
B. Bowerman ◽  
M.K. Ingram ◽  
C.P. Hunter
Keyword(s):  
Cell Fate ◽  
Expression Patterns ◽  
Control Cell ◽  
Gene Products ◽  
Cell Fate Specification ◽  
Loss Of Function ◽  
C Elegans ◽  
Embryonic Polarity ◽  
Early Embryos ◽  
Anterior Posterior

After fertilization in C. elegans, activities encoded by the maternally expressed par genes appear to establish cellular and embryonic polarity. Loss-of-function mutations in the par genes disrupt anterior-posterior (a-p) asymmetries in early embryos and result in highly abnormal patterns of cell fate. Little is known about how the early asymmetry defects are related to the cell fate patterning defects in par mutant embryos, or about how the par gene products affect the localization and activities of developmental regulators known to specify the cell fate patterns made by individual blastomeres. Examples of such regulators of blastomere identity include the maternal proteins MEX-3 and GLP-1, expressed at high levels anteriorly, and SKN-1 and PAL-1, expressed at high levels posteriorly in early embryos. To better define par gene functions, we examined the expression patterns of MEX-3, PAL-1 and SKN-1, and we analyzed mex-3, pal-1, skn-1 and glp-1 activities in par mutant embryos. We have found that mutational inactivation of each par gene results in a unique phenotype, but in no case do we observe a complete loss of a-p asymmetry. We conclude that no one par gene is required for all a-p asymmetry and we suggest that, in some cases, the par genes act independently of each other to control cell fate patterning and polarity. Finally, we discuss the implications of our findings for understanding how the initial establishment of polarity in the zygote by the par gene products leads to the proper localization of more specifically acting regulators of blastomere identity.

scholarly journals Cryptic genetic variation in a heat shock protein shapes the expressivity of a mutation affecting stem cell behaviour in C. elegans

2020 ◽  
Author(s):  
Sneha L. Koneru ◽  
Mark Hintze ◽  
Dimitris Katsanos ◽  
Michalis Barkoulas
Keyword(s):  
Genetic Variation ◽  
Stem Cell ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Cell Fate ◽  
Single Amino Acid ◽  
Cryptic Genetic Variation ◽  
C Elegans ◽  
Seam Cell ◽  
The Difference

AbstractA fundamental question in medical genetics is how the genetic background modifies the phenotypic outcome of key mutations. We address this question by focusing on the epidermal seam cells, which display stem cell properties in Caenorhabditis elegans. We demonstrate that a null mutation in the GATA transcription factor egl-18, which is involved in seam cell fate maintenance, is more tolerated and thus has lower expressivity in the divergent CB4856 isolate from Hawaii than the lab reference strain N2 from Bristol. We identify multiple quantitative trait loci (QTLs) underlying the difference in mutation expressivity between the two isolates. These QTLs reveal cryptic genetic variation, which acts to reinforce seam cell fate through potentiating Wnt signalling. Within one QTL region, a single amino acid deletion in the heat shock protein HSP-110 in CB4856 lowers egl-18 mutation expressivity. Our work underscores that natural variation in conserved heat shock proteins can shape mutation expressivity.

scholarly journals Regulation of nuclear-cytoplasmic partitioning by the lin-28-lin-46 pathway reinforces microRNA repression of HBL-1 to confer robust cell-fate progression in C. elegans

2019 ◽  
Author(s):  
Orkan Ilbay ◽  
Victor Ambros
Keyword(s):  
Cell Fate ◽  
Translational Regulation ◽  
Rna Binding ◽  
Nuclear Accumulation ◽  
Synthesis Rate ◽  
Microrna Target ◽  
Cell Fates ◽  
Down Regulation ◽  
C Elegans ◽  
Necessary And Sufficient

AbstractMicroRNAs target complementary mRNAs for degradation or translational repression, reducing or preventing protein synthesis. In C. elegans, the transcription factor HBL-1 (Hunchback-like 1) promotes early larval (L2) stage cell-fate, and the let-7-family microRNAs temporally down-regulate HBL-1 to enable the L2-to-L3 cell-fate progression. In parallel to let-7-family microRNAs, the conserved RNA binding protein LIN-28 and its downstream gene lin-46, also act upstream of HBL-1 in regulating the L2-to-L3 cell-fate progression. The molecular function of LIN-46, and how the lin-28-lin-46 pathway regulates HBL-1, are not understood. Here, we report that the regulation of HBL-1 by the lin-28-lin-46 pathway is independent of the let-7/lin-4 microRNA complementary sites (LCSs) in the hbl-1 3’UTR, and involves a stage-specific post-translational regulation of HBL-1 nuclear accumulation. We find that LIN-46 is necessary and sufficient to prevent nuclear accumulation of HBL-1. Our results illuminate that the robust progression from L2 to L3 cell-fates depends on the combination of two distinct modes of HBL-1 down-regulation: decreased synthesis of HBL-1 via let-7-family microRNA activity, and decreased nuclear accumulation of HBL-1 via action of the lin-28-lin-46 pathway. Like HBL-1, many microRNA targets are transcription factors (TFs); and cooperation between regulation of nuclear accumulation and microRNA-mediated control of synthesis rate may be required to increase the precision of or confer robustness to down-regulation of these microRNA target TFs, which can be critical to achieve the optimal phenotypes.

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