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.

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.

Caenorhabditis elegans lin-25: cellular focus, protein expression and requirement for sur-2 during induction of vulval fates

Development ◽  
1998 ◽  
Vol 125 (23) ◽  
pp. 4809-4819 ◽  
Author(s):  
L. Nilsson ◽  
X. Li ◽  
T. Tiensuu ◽  
R. Auty ◽  
I. Greenwald ◽  
...  
Keyword(s):  
Protein Expression ◽  
Map Kinase ◽  
Signal Transduction Pathway ◽  
Precursor Cells ◽  
C Elegans ◽  
Novel Proteins ◽  
Genetic Mosaic ◽  
Mosaic Analysis ◽  
Map Kinase Pathway ◽  
Cell Fusions

Induction of vulval fates in the C. elegans hermaphrodite is mediated by a signal transduction pathway involving Ras and MAP kinase. Previous genetic analysis has suggested that two potential targets of this pathway in the vulva precursor cells are two novel proteins, LIN-25 and SUR-2. In this report, we describe further studies of lin-25. The results of a genetic mosaic analysis together with those of experiments in which lin-25 was expressed under the control of an heterologous promoter suggest that the major focus of lin-25 during vulva induction is the vulva precursor cells themselves. We have generated antisera to LIN-25 and used these to analyse the pattern of protein expression. LIN-25 is present in all six precursor cells prior to and during vulva induction but later becomes restricted to cells of the vulval lineages. Mutations in genes in the Ras/MAP kinase pathway do not affect the pattern of expression but the accumulation of LIN-25 is reduced in the absence of sur-2. Overexpression of LIN-25 does not rescue sur-2 mutant defects suggesting that LIN-25 and SUR-2 may function together. LIN-25 is also expressed in the lateral hypodermis. Overexpression of LIN-25 disrupts lateral hypodermal cell fusion, suggesting that lin-25 may play a role in regulating cell fusions in C. elegans.

Specificity of TGFbeta signaling is conferred by distinct type I receptors and their associated SMAD proteins in Caenorhabditis elegans

Development ◽  
1999 ◽  
Vol 126 (2) ◽  
pp. 251-260 ◽  
Author(s):  
S. Krishna ◽  
L.L. Maduzia ◽  
R.W. Padgett
Keyword(s):  
Body Size ◽  
Receptor Tyrosine Kinase ◽  
Distinct Type ◽  
General Mechanism ◽  
Type I ◽  
Biological Functions ◽  
Signaling Specificity ◽  
C Elegans ◽  
Reduced Body ◽  
Smad Proteins

In C. elegans, the TGFbeta-like type II receptor daf-4 is required for two distinct signaling pathways. In association with the type I receptor daf-1, it functions in the dauer pathway. In addition, it is also required for body size determination and male tail patterning, roles which do not require daf-1. In an effort to determine how two different signals are transmitted through daf-4, we looked for other potential signaling partners for DAF-4. We have cloned and characterized a novel type I receptor and show that it is encoded by sma-6. Mutations in sma-6 generate the reduced body size (Sma) and abnormal mail tail (Mab) phenotypes identical to those observed in daf-4 and sma-2, sma-3, sma-4 mutants (C. elegans Smads), indicating that they function in a common signaling pathway. However, mutations in sma-6, sma-2, sma-3, or sma-4 do not produce constitutive dauers, which demonstrates that the unique biological functions of daf-4 are mediated by distinct type I receptors functioning in parallel pathways. We propose that the C. elegans model for TGFbeta-like signaling, in which distinct type I receptors determine specificity, may be a general mechanism of achieving specificity in other organisms. These findings distinguish between the manner in which signaling specificity is achieved in TGFbeta-like pathways and receptor tyrosine-kinase (RTK) pathways.

scholarly journals Akirin Is Required for Muscle Function and Acts Through the TGF-β Sma/Mab Signaling Pathway in Caenorhabditis elegans Development

2019 ◽  
Vol 10 (1) ◽  
pp. 387-400 ◽  
Author(s):  
Richard Bowman ◽  
Nathan Balukoff ◽  
Amy Clemons ◽  
Emily Koury ◽  
Talitha Ford ◽  
...  
Keyword(s):  
Body Size ◽  
Caenorhabditis Elegans ◽  
Signaling Pathway ◽  
Chromatin Remodeling ◽  
Muscle Development ◽  
The Body ◽  
Model Systems ◽  
Loss Of Function ◽  
C Elegans ◽  
Chromatin Remodeling Complex

Akirin, a conserved metazoan protein, functions in muscle development in flies and mice. However, this was only tested in the rodent and fly model systems. Akirin was shown to act with chromatin remodeling complexes in transcription and was established as a downstream target of the NFκB pathway. Here we show a role for Caenorhabditis elegans Akirin/AKIR-1 in the muscle and body length regulation through a different pathway. Akirin localizes to somatic tissues throughout the body of C. elegans, including muscle nuclei. In agreement with its role in other model systems, Akirin loss of function mutants exhibit defects in muscle development in the embryo, as well as defects in movement and maintenance of muscle integrity in the C. elegans adult. We also have determined that Akirin acts downstream of the TGF-β Sma/Mab signaling pathway in controlling body size. Moreover, we found that the loss of Akirin resulted in an increase in autophagy markers, similar to mutants in the TGF-β Sma/Mab signaling pathway. In contrast to what is known in rodent and fly models, C. elegans Akirin does not act with the SWI/SNF chromatin-remodeling complex, and is instead involved with the NuRD chromatin remodeling complex in both movement and regulation of body size. Our studies define a novel developmental role (body size) and a new pathway (TGF-β Sma/Mab) for Akirin function, and confirmed its evolutionarily conserved function in muscle development in a new organism.

scholarly journals Mosaic Analysis Using a ncl-1 (+) Extrachromosomal Array Reveals That lin-31 Acts in the Pn.p Cells During Caenorhabditis elegans Vulval Development

Genetics ◽  
1996 ◽  
Vol 143 (3) ◽  
pp. 1181-1191 ◽  
Author(s):  
Leilani M Miller ◽  
David A Waxing ◽  
Stuart K Kim
Keyword(s):  
Caenorhabditis Elegans ◽  
The Body ◽  
Specific Cell ◽  
Vulval Development ◽  
C Elegans ◽  
Genetic Mosaic ◽  
Extrachromosomal Array ◽  
Mosaic Analysis ◽  
Putative Transcription Factor ◽  
Sites Of Action

Abstract We describe a genetic mosaic analysis procedure in which Caenorhabditis elegans mosaics are generated by spontaneous loss of an extrachromosomal array. This technique allows almost any C. elegans gene that can be used in germline transformation experiments to be used in mosaic analysis experiments. We identified a cosmid clone that rescues the mutant phenotype of ncl-1, so that this cell-autonomous marker could be used to analyze mosaic animals. To determine the sites of action for unc-29 and lin-31, an extrachromosomal array was constructed containing the ncl-1(+) cosmid linked to lin-31(+) and unc-29(+) cosmids. This array is mitotically unstable and can be lost to produce a clone of mutant cells. The specific cell division at which the extrachromosomal array had been lost was deduced by scoring the Ncl phenotypes of individual cells in genetic mosaics. The Unc-29 and Lin-31 phenotypes were then scored in these animals to determine in which cells these genes are required. This analysis showed that unc-29, which encodes a subunit of the acetylcholine receptor, acts in the body muscle cells. Furthermore, lin-31, which specifies cell fates during vulval induction and encodes a putative transcription factor similar to HNF-3/fork head, acts in the Pn.p cells

scholarly journals Systematic Functional Characterization of Human 21st Chromosome Orthologs in Caenorhabditis elegans

2017 ◽  
Author(s):  
Sarah K. Nordquist ◽  
Sofia R. Smith ◽  
Jonathan T. Pierce
Keyword(s):  
Nervous System ◽  
Down Syndrome ◽  
Caenorhabditis Elegans ◽  
Functional Characterization ◽  
System Function ◽  
Loss Of Function ◽  
C Elegans ◽  
Genes Encoding ◽  
Nervous System Function ◽  
Encoding Protein

ABSTRACTIndividuals with Down syndrome have neurological and muscle impairments due to an additional copy of the human 21st chromosome (HSA21). Only a few of ~200 HSA21 genes encoding protein have been linked to specific Down syndrome phenotypes, while the remainder are understudied. To identify poorly characterized HSA21 genes required for nervous system function, we studied behavioral phenotypes caused by loss-of-function mutations in conserved HSA21 orthologs in the nematode Caenorhabditis elegans. We identified ten HSA21 orthologs that are required for neuromuscular behaviors: cle-1 (COL18A1), cysl-2 (CBS), dnsn-1 (DONSON), eva-1 (EVA1C), mtq-2 (N6ATM1), ncam-1 (NCAM2), pad-2 (POFUT2), pdxk-1 (PDXK), rnt-1 (RUNX1), and unc-26 (SYNJ1). We also found that three of these genes are required for normal release of the neurotransmitter acetylcholine. This includes a known synaptic gene unc-26 (SYNJ1), as well as uncharacterized genes pdxk-1 (PDXK) and mtq-2 (N6ATM1). As the first systematic functional analysis of HSA21 orthologs, this study may serve as a platform to understand genes that underlie phenotypes associated with Down syndrome.ARTICLE SUMMARYDown syndrome causes neurological and muscle dysfunction due to an extra 21st chromosome. This chromosome has over 200 genes, most of which are understudied. To address this, we studied whether reducing function of these gene equivalents in the worm C. elegans caused neuronal or muscle defects. We identified ten genes conserved between human and worm that mediate function of behaviors. Among these, we show the uncharacterized genes mtq-2 and pdxk-1 are important for synaptic transmission and are exclusively expressed in nervous system. Our analysis may reveal functions of poorly studied genes that affect nervous system function in Down syndrome.

Genetic mosaic analysis in the nervous system

2004 ◽  
Vol 14 (5) ◽  
pp. 647-653 ◽  
Author(s):  
Christopher T Zugates ◽  
Tzumin Lee
Keyword(s):  
Nervous System ◽  
Genetic Mosaic ◽  
Mosaic Analysis

A BMP homolog acts as a dose-dependent regulator of body size and male tail patterning in Caenorhabditis elegans

Development ◽  
1999 ◽  
Vol 126 (2) ◽  
pp. 241-250 ◽  
Author(s):  
Y. Suzuki ◽  
M.D. Yandell ◽  
P.J. Roy ◽  
S. Krishna ◽  
C. Savage-Dunn ◽  
...  
Keyword(s):  
Body Size ◽  
Caenorhabditis Elegans ◽  
Expression Pattern ◽  
Genetic Interactions ◽  
Loss Of Function ◽  
Male Tail ◽  
C Elegans ◽  
Reduced Body ◽  
Smad Signaling Pathway ◽  
Dose Dependent

We cloned the dbl-1 gene, a C. elegans homolog of Drosophila decapentaplegic and vertebrate BMP genes. Loss-of-function mutations in dbl-1 cause markedly reduced body size and defective male copulatory structures. Conversely, dbl-1 overexpression causes markedly increased body size and partly complementary male tail phenotypes, indicating that DBL-1 acts as a dose-dependent regulator of these processes. Evidence from genetic interactions indicates that these effects are mediated by a Smad signaling pathway, for which DBL-1 is a previously unidentified ligand. Our study of the dbl-1 expression pattern suggests a role for neuronal cells in global size regulation as well as male tail patterning.

scholarly journals The NALCN Channel Regulator UNC-80 Functions in a Subset of Interneurons To Regulate Caenorhabditis elegans Reversal Behavior

2019 ◽  
Vol 10 (1) ◽  
pp. 199-210 ◽  
Author(s):  
Chuanman Zhou ◽  
Jintao Luo ◽  
Xiaohui He ◽  
Qian Zhou ◽  
Yunxia He ◽  
...  
Keyword(s):  
Plant Hormone ◽  
Neuronal Excitability ◽  
Resting Membrane Potential ◽  
Loss Of Function ◽  
Wild Type ◽  
C Elegans ◽  
Link Type ◽  
Complex Functions ◽  
And Function ◽  
Multiple Loss

NALCN (Na+leak channel, non-selective) is a conserved, voltage-insensitive cation channel that regulates resting membrane potential and neuronal excitability. UNC79 and UNC80 are key regulators of the channel function. However, the behavioral effects of the channel complex are not entirely clear and the neurons in which the channel functions remain to be identified. In a forward genetic screen for C. elegans mutants with defective avoidance response to the plant hormone methyl salicylate (MeSa), we isolated multiple loss-of-function mutations in unc-80 and unc-79. C. elegans NALCN mutants exhibited similarly defective MeSa avoidance. Interestingly, NALCN, unc-80 and unc-79 mutants all showed wild type-like responses to other attractive or repelling odorants, suggesting that NALCN does not broadly affect odor detection or related forward and reversal behaviors. To understand in which neurons the channel functions, we determined the identities of a subset of unc-80-expressing neurons. We found that unc-79 and unc-80 are expressed and function in overlapping neurons, which verified previous assumptions. Neuron-specific transgene rescue and knockdown experiments suggest that the command interneurons AVA and AVE and the anterior guidepost neuron AVG can play a sufficient role in mediating unc-80 regulation of the MeSa avoidance. Though primarily based on genetic analyses, our results further imply that MeSa might activate NALCN by direct or indirect actions. Altogether, we provide an initial look into the key neurons in which the NALCN channel complex functions and identify a novel function of the channel in regulating C. elegans reversal behavior through command interneurons.

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