The <i>C. elegans tailless/Tlx</i> homolog <i>nhr-67</i> regulates a stage-specific program of linker cell migration in male gonadogenesis

Kato, Mihoko; Sternberg, Paul W.

doi:10.1242/dev.035477

Cited by 22 publications

(29 citation statements)

References 61 publications

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“…Feeding RNAi was carried out as in ref. 3. Worms were scored for LC defects by Nomarski microscopy, allowing more detailed screening than dissection microscopy previously used (3).…”

Section: Methodsmentioning

confidence: 99%

“…1A). During 25 h of the second to fourth larval stages (L2 through L4), the LC moves anteriorly along the ventral body wall, turns dorsally, proceeds posteriorly, switches sides once more to the ventral bodywall, continues posteriorward, reaches the cloaca, and eventually dies (2)(3)(4). Throughout this process, the proliferating and lengthening male gonad follows the LC's path to the cloaca.…”

mentioning

confidence: 99%

“…A YFP transgene of srsx-18 recapitulated the results of the RNA-seq, with reporter activity in L4 LCs that was abolished by nhr-67(RNAi). srsx-18(RNAi) causes delayed migration, which is one of nhr-67's RNAi phenotypes (3). srsx-18 may therefore be both a direct target of NHR-67 and a biologically important effector of NHR-67 in LCs.…”

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confidence: 99%

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Functional transcriptomics of a migrating cell in Caenorhabditis elegans

Schwarz

Kato

Sternberg

2012

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

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In both metazoan development and metastatic cancer, migrating cells must carry out a detailed, complex program of sensing cues, binding substrates, and moving their cytoskeletons. The linker cell in Caenorhabditis elegans males undergoes a stereotyped migration that guides gonad organogenesis, occurs with precise timing, and requires the nuclear hormone receptor NHR-67. To better understand how this occurs, we performed RNA-seq of individually staged and dissected linker cells, comparing transcriptomes from linker cells of third-stage (L3) larvae, fourth-stage (L4) larvae, and nhr-67-RNAi-treated L4 larvae. We observed expression of 8,000-10,000 genes in the linker cell, 22-25% of which were up-or downregulated 20-fold during development by NHR-67. Of genes that we tested by RNAi, 22% (45 of 204) were required for normal shape and migration, suggesting that many NHR-67-dependent, linker cell-enriched genes play roles in this migration. One unexpected class of genes up-regulated by NHR-67 was tandem pore potassium channels, which are required for normal linker-cell migration. We also found phenotypes for genes with human orthologs but no previously described migratory function. Our results provide an extensive catalog of genes that act in a migrating cell, identify unique molecular functions involved in nematode cell migration, and suggest similar functions in humans.major sperm protein | nematode development | transcriptional profiling | twin pore potassium channels | conserved uncharacterized proteins C ell migration is pervasive in animal development and is also an unwanted part of human cancer. Several different varieties of cell migration, ranging from social protozoa to the human immune system, have been extensively studied (1), but there remains a need for detailed analysis of the different components of migration in a simple cell type that can be exhaustively probed through anatomy, genetics, and genomics. We have undertaken to develop the linker cell (LC) of Caenorhabditis elegans as such a model. The LC is a single cell, attached to the front of a proliferating male gonad, which carries out a stereotypic, long-range migration to generate the shape of the mature gonad (Fig. 1A). During 25 h of the second to fourth larval stages (L2 through L4), the LC moves anteriorly along the ventral body wall, turns dorsally, proceeds posteriorly, switches sides once more to the ventral bodywall, continues posteriorward, reaches the cloaca, and eventually dies (2-4). Throughout this process, the proliferating and lengthening male gonad follows the LC's path to the cloaca. Stage-specific changes occur during the middle to late stages of migration (L3 and L4 larval stages): the LC changes shape from a spheroid to a pointed ellipsoid; it increases its speed of migration; and the netrin receptor gene unc-5 is down-regulated within the LC, which causes it to switch body walls ventrally ( Fig. 1A; ref. 3). These changes between the L3 and L4 stages require the orphan nuclear receptor NHR-67, whose orthologs TAILLESS and TLX...

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“…Feeding RNAi was carried out as in ref. 3. Worms were scored for LC defects by Nomarski microscopy, allowing more detailed screening than dissection microscopy previously used (3).…”

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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Functional transcriptomics of a migrating cell in Caenorhabditis elegans

Schwarz

Kato

Sternberg

2012

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

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“…NHR-67 regulates the migration of the male linker cell (as a cellautonomous, stage-specific regulator of timing in linker cell migration programs during L3 and L4 stage) [110]. The linker cell in C. elegans males undergoes a stereotyped migration that guides gonad organogenesis.…”

Section: Nr2e-tlx/tllmentioning

confidence: 99%

“…It occurs with precise timing. NHR-67 is required for this event [110]. Whole transcriptome expression analysis of a linker cell inhibited for NHR-67 by RNAi identified 22-25% of 10,000 analyzed genes as upor down-regulated (20-fold) [111].…”

Section: Nr2e-tlx/tllmentioning

confidence: 99%

Nuclear receptors in nematode development: Natural experiments made by a phylum

Kostrouch

2015

Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanism

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Natural reversal of left‐right gut/gonad asymmetry in C. elegans males is independent of embryonic chirality

Callander

Alcorn

Birsoy

et al. 2014

Genesis

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Anatomical left-right (L/R) handedness asymmetry in C. elegans is established in the four-cell embryo as a result of anteroposterior skewing of transverse mitotic spindles with a defined handedness. This event creates a chiral embryo and ultimately an adult body plan with fixed L/R positioning of internal organs and components of the nervous system. While this “dextral” configuration is invariant in hermaphrodites, it can be reversed by physical manipulation of the early embryo or by mutations that interfere with mitotic spindle orientation, which leads to viable, mirror-reversed (sinistral) animals. During normal development of the C. elegans male, the gonad develops on the right of the midline, with the gut bilaterally apposed on the left. However, we found that in males of the laboratory N2 strain and Hawaiian (“Hw”) wild isolate, the gut/gonad asymmetry is frequently reversed in a temperature-dependent manner, independent of normal embryonic chirality. We also observed sporadic errors in gonad migration occurring naturally during early larval stages of these and other wild strains; however, the incidence of such errors does not correlate with the frequency of L/R gut/gonad reversals in these strains. Analysis of N2/Hw hybrids and recombinant inbred advanced intercross lines (RIAILs) indicate that the L/R organ reversals are likely to result from recessively acting variations in multiple genes. Thus, unlike the highly reproducible L/R asymmetries of most structures in hermaphrodites, the L/R asymmetry of the male C. elegans body plan is less rigidly determined and subject to natural variation that is influenced by a multiplicity of genes.

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The C. elegans tailless/Tlx homolog nhr-67 regulates a stage-specific program of linker cell migration in male gonadogenesis

Cited by 22 publications

References 61 publications

Functional transcriptomics of a migrating cell in Caenorhabditis elegans

Functional transcriptomics of a migrating cell in Caenorhabditis elegans

Nuclear receptors in nematode development: Natural experiments made by a phylum

Natural reversal of left‐right gut/gonad asymmetry in C. elegans males is independent of embryonic chirality

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