Modulation of EGF receptor-mediated vulva development by the heterotrimeric G-protein Gαq and excitable cells in<i>C</i>.<i>elegans</i>

Moghal, Nadeem; García, L. René; Khan, Liakot A.; Iwasaki, Kouichi; Sternberg, Paul W.

doi:10.1242/dev.00670

Cited by 32 publications

(77 citation statements)

References 80 publications

(84 reference statements)

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“…These observations suggest that the mot͞med12 gene plays a regulatory role in vertebrate neuronal development. Consistent with this notion, it is interesting to mention that Caenorhabditis elegans (22)(23)(24)(25) and Drosophila (26,27) mutants in med12 also display specific phenotypes, and human polymorphisms in med12͞hopa correlate with distinct brain diseases such as schizophrenia and hypothyroidism (28).…”

Section: Discussionmentioning

confidence: 79%

A subunit of the mediator complex regulates vertebrate neuronal development

Wang

Yang

Uno

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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The unique profiles of gene expression dictate distinct cellular identity. How these profiles are established during development is not clear. Here we report that the mutant motionless (mot), identified in a genetic screen for mutations that affect neuronal development in zebrafish, displays deficits of monoaminergic neurons and cranial sensory ganglia, whereas expression of the panneuronal marker Hu is largely unperturbed; GABAergic and subsets of cranial motor neurons do not appear to be deficient. Positional cloning reveals that mot encodes Med12, a component of the evolutionarily conserved Mediator complex, whose in vivo function is not well understood in vertebrates. mot͞med12 transcripts are enriched in the embryonic brain and appear distinct from two other Mediator components Med17 and Med21. Delivery of human med12 RNA into zebrafish restores normality to the mot mutant and, strikingly, leads to premature neuronal differentiation and an increased production of monoaminergic neuronal subtypes in WT. Further investigation reveals that mot͞med12 is necessary to regulate, and when overexpressed is capable of increasing, the expression of distinct neuronal determination genes, including zash1a and lim1, and serves as an in vivo cofactor for Sox9 in this process. Together, our analyses reveal a regulatory role of Mot͞ Med12 in vertebrate neuronal development. D uring vertebrate development, pluripotent stem cells respond to spatially localized signals that regulate their cell cycle exit and subsequent differentiation into specialized cell types. The central nervous system contains a large number of different cell types and has been an organ of interest for studying progenitor cell commitment͞differentiation and the generation of cellular diversity (1, 2). In addition to spatial control, temporal regulation of neuronal development has been appreciated but is much less understood in the vertebrate nervous system (3, 4). It is widely accepted that progenitor cells need to establish unique profiles of gene expression that dictate their final destiny. Intracellular pathways underlying the establishment of precise gene expression patterns in the developing nervous system are not well understood.We have undertaken a genetic approach to characterize genes and pathways that control vertebrate neuronal development by using zebrafish as a model system (5-8). Here, we describe the molecular characterization of the motionless (mot) mutant isolated from our genetic screen. The mot mutant embryos have defects in movement and neuronal and cardiovascular development (9). Current analyses reveal that they have normal brain patterning and do not suffer a global deficit of neurons as evidenced by largely unperturbed expression of the pan-neuronal marker Hu. However, the mot mutant exhibits deficits in neuronal subtypes that include monoaminergic (MA) neurons [forebrain dopaminergic and serotonergic (5HT) neurons, hindbrain noradrenergic (NA) and 5HT neurons, and neural-crest derived sympathetic neurons] and cranial sensory gangli...

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Section: Discussionmentioning

confidence: 79%

A subunit of the mediator complex regulates vertebrate neuronal development

Wang

Yang

Uno

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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“…However, because egl-19 has been shown to be involved in worm development (Tam et al, 2000;Moghal et al, 2003;Bauer Huang et al, 2007), a developmental failure could also explain the shorter size of the gain-of-function mutants. To test whether egl-19(gf ) mutants are indeed hypercontracted, we carried out a set of pharmacological tests, adapted from Petzold et al (Petzold et al, 2011).…”

Section: Egl-19(gf) Phenotype Results From a High Muscle Tonementioning

confidence: 99%

Hyperactivation of L-type voltage-gated Ca2+ channels in C. elegans striated muscle can result from point mutations in the IS6 or the IIIS4 segment of the α1 subunit.

Lainé

Ségor

Zhan

et al. 2014

Journal of Experimental Biology

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Several human diseases, including hypokalemic periodic paralysis and Timothy syndrome, are caused by mutations in voltage-gated calcium channels. The effects of these mutations are not always well understood, partially because of difficulties in expressing these channels in heterologous systems. The use of Caenorhabditis elegans could be an alternative approach to determine the effects of mutations on voltage-gated calcium channel function because all the main types of voltage-gated calcium channels are found in C. elegans, a large panel of mutations already exists and efficient genetic tools are available to engineer customized mutations in any gene. In this study, we characterize the effects of two gain-of-function mutations in egl-19, which encodes the L-type calcium channel α 1 subunit. One of these mutations, ad695, leads to the replacement of a hydrophobic residue in the IIIS4 segment. The other mutation, n2368, changes a conserved glycine of IS6 segment; this mutation has been identified in patients with Timothy syndrome. We show that both egl-19 (gain-of-function) mutants have defects in locomotion and morphology that are linked to higher muscle tone. Using in situ electrophysiological approaches in striated muscle cells, we provide evidence that this high muscle tone is due to a shift of the voltage dependency towards negative potentials, associated with a decrease of the inactivation rate of the L-type Ca 2+ current. Moreover, we show that the maximal conductance of the Ca 2+ current is decreased in the strongest mutant egl-19(n2368), and that this decrease is correlated with a mislocalization of the channel.

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“…The wild-type reference strain used was N2 Bristol (Brenner, 1974). We also used the following alleles in this study: egl-30(tg26gf) (Moghal et al, 2003), unc-75(e95) (Brenner, 1974), sy558 males that spontaneously protract their spicules, we separated L4 males from hermaphrodites to a plate seeded with Escherichia coli OP50. Twenty-four hours later, we scored the males for the protraction constitutive (Prc) phenotype with a Wild M5A microscope.…”

Section: Methodsmentioning

confidence: 99%

Integration of Male Mating and Feeding Behaviors inCaenorhabditis elegans

Gruninger¹,

Gualberto²,

LeBoeuf³

et al. 2006

J. Neurosci.

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The Caenorhabditis elegans male must integrate various environmental cues to ensure proper execution of mating. One step of male mating, the insertion of the male copulatory spicules into its mate, requires UNC-103 ERG (ether-a-go-go-related gene)-like K ϩ channels. unc-103(lf) alleles cause males to protract their spicules spontaneously in the absence of mating cues. To identify proteins that work with UNC-103, we suppressed unc-103(lf) and isolated lev-11(rg1). LEV-11 (tropomyosin) regulates the spicules directly by controlling the male sex muscles and indirectly by controlling the pharyngeal muscles. lev-11-mediated suppression requires the pharyngeal NSM neurosecretory motor neurons; ablating these neurons in lev-11(rg1); unc-103(lf) males restores spontaneous spicule protraction. Additionally, unc-103-induced spicule protraction can be suppressed by reducing a pharyngeal-specific troponin T. These observations demonstrate that non-genitalia cells involved in feeding also mediate male sexual behaviors.

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Modulation of EGF receptor-mediated vulva development by the heterotrimeric G-protein Gαq and excitable cells inC.elegans

Cited by 32 publications

References 80 publications

A subunit of the mediator complex regulates vertebrate neuronal development

A subunit of the mediator complex regulates vertebrate neuronal development

Hyperactivation of L-type voltage-gated Ca2+ channels in C. elegans striated muscle can result from point mutations in the IS6 or the IIIS4 segment of the α1 subunit.

Integration of Male Mating and Feeding Behaviors inCaenorhabditis elegans

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