Crosstalk between a Nuclear Receptor and β-Catenin Signaling Decides Cell Fates in the C. elegans Somatic Gonad

The invariant development of free-living nematodes combined with the extensive knowledge of Caenorhabditis elegans developmental biology provides an experimental system for an analysis of the evolution of developmental mechanisms. We have collected a number of new nematode species from soil samples. Most are easily cultured and their development can be analyzed at the level of individual cells using techniques standard to Caenorhabditis. So far, we have focused on differences in the development of the vulva among species of the families Rhabditidae and Panagrolaimidae. Preceding vulval development, twelve Pn cells migrate into the ventral cord and divide to produce posterior daughters [Pn.p cells] whose fates vary in a position specific manner [from P1.p anterior to P12.p posterior]. In C. elegans hermaphrodites, P(3-8).p are tripotent and form an equivalence group. These cells can express either of two vulval fates (1° or 2°) in response to a signal from the anchor cell of the somatic gonad, or a non-vulval fate (3°), resulting in a 3°-3°-2°-1°-2°-3° pattern of cell fates. Evolutionary differences in vulval development include the number of cells in the vulval equivalence group, the number of 1° cells, the number of progeny generated by each vulval precursor cell, and the position of VPCs before morphogenesis. Examples of three Rhabditidae genera have a posterior vulva in the position of P9-P11 ectoblasts. In Cruznema tripartitum, P(5-7).p form the vulva as in Caenorhabditis, but they migrate posteriorly before dividing. Induction occurs after the gonad grows posteriorly to the position of P(5-7).p cells. In two other species, Mesorhabditis sp. PS 1179 and Teratorhabditis palmarum, we have found changes in induction and competence with respect to their presumably more C. elegans-like ancestor. In Mesorhabditis, P(5-7).p form the vulva after migrating to a posterior position. However, the gonad is not required to specify the pattern of cell fates 3°-2°-1°-2°-3°. Moreover, the Pn.p cells are not equivalent in their potentials to form the vulva. A regulatory constraint in this family thus forces the same set of precursors to generate the vulva, rather than more appropriately positioned Pn.p cells.

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The C. elegans heterochronic gene lin-28 coordinates the timing of hypodermal and somatic gonadal programs for hermaphrodite reproductive system morphogenesis

10.1101/265314 ◽

2018 ◽

Author(s):

Sungwook Choi ◽

Victor Ambros

Keyword(s):

Control Cell ◽

Gonad Development ◽

Developmental Timing ◽

Specific Cell ◽

Cell Fates ◽

C Elegans ◽

Gonad Morphology ◽

Somatic Gonad ◽

Heterochronic Gene ◽

A Cell

AbstractC. elegans heterochronic genes determine the timing of expression of specific cell fates in particular stages of developing larva. However, their broader roles in coordinating developmental events across diverse tissues has been less well investigated. Here, we show that loss of lin-28, a central heterochronic regulator of hypodermal development, causes reduced fertility associated with abnormal somatic gonad morphology. In particular, the abnormal spermatheca-uterine valve morphology of lin-28(lf) hermaphrodites trap embryos in the spermatheca, which disrupts ovulation and causes embryonic lethality. The same genes that act downstream of lin-28 in the regulation of hypodermal developmental timing also act downstream of lin-28 in somatic gonad morphogenesis and fertility. Importantly, we find that hypodermal expression, but not somatic gonadal expression, of lin-28 is sufficient for restoring normal somatic gonad morphology in lin-28(lf) mutants. We propose that the abnormal somatic gonad morphogenesis of lin-28(lf) hermaphrodites results from temporal discoordination between the accelerated hypodermal development and normally timed somatic gonad development. Thus, our findings exemplify how a cell-intrinsic developmental timing program can also control cell non-autonomous signaling critical for proper development of other interacting tissues.

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Evolution of Sex Determination in Caenorhabditis: Unusually High Divergence of tra-1 and Its Functional Consequences

Genetics ◽

10.1093/genetics/144.2.587 ◽

1996 ◽

Vol 144 (2) ◽

pp. 587-595 ◽

Cited By ~ 5

Author(s):

Mario de Bono ◽

Jonathan Hodgkin

Keyword(s):

Sex Determination ◽

Germ Line ◽

Amino Acid Identity ◽

Evolution Of Sex ◽

Phenotypic Differences ◽

C Elegans ◽

Functional Studies ◽

Somatic Gonad ◽

Functional Consequences ◽

Significant Divergence

Abstract The tra-1 gene is a terminal regulator of somatic sex in Caenorhabditis elegans: high tra-1 activity elicits female development, low tra-1 activity elicits male development. To investigate the function and evolution of tra-1, we examined the tra-1 gene from the closely related nematode C. briggsae. Ce-tra-1 and Cb-tra-1 are unusually divergent. Each gene generates two transcripts, but only one of these is present in both species. This common transcript encodes TRA-1A, which shows only 44% amino acid identity between the species, a figure much lower than that for previously compared genes. A Cb-tra-1 transgene rescues many tissues of tra-1(nul1) mutants of C. elegans but not the somatic gonad or germ line. This transgene also causes nongonadal feminization of XO animals, indicating incorrect sexual regulation. Alignment of Ce-TRA-1A and Cb-TRA-1A defines several conserved regions likely to be important for tra-1 function. The phenotypic differences between Ce-tra-1(null) mutants rescued by Cb-tra-1 transgenes and wild-type C. elegans indicate significant divergence of regulatory regions. These molecular and functional studies suggest that evolution of sex determination in nematodes is rapid and genetically complex.

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lin-35/Rb and xnp-1/ATR-X function redundantly to control somatic gonad development in C. elegans

Developmental Biology ◽

10.1016/j.ydbio.2004.06.009 ◽

2004 ◽

Vol 273 (2) ◽

pp. 335-349 ◽

Cited By ~ 23

Author(s):

Aaron M. Bender ◽

Orion Wells ◽

David S. Fay

Keyword(s):

Gonad Development ◽

C Elegans ◽

Somatic Gonad

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hlh-12, a gene that is necessary and sufficient to promote migration of gonadal regulatory cells in C. elegans, evolved within the Caenorhabditis clade

Genetics ◽

10.1093/genetics/iyab127 ◽

2021 ◽

Author(s):

Hana E Littleford ◽

Karin Kiontke ◽

David H A Fitch ◽

Iva Greenwald

Keyword(s):

Ectopic Expression ◽

Morphological Diversity ◽

Nematode Species ◽

Bhlh Protein ◽

Vulval Development ◽

C Elegans ◽

Form And Function ◽

Somatic Gonad ◽

And Function ◽

Necessary And Sufficient

Abstract Specialized cells of the somatic gonad primordium of nematodes play important roles in the final form and function of the mature gonad. C. elegans hermaphrodites are somatic females that have a two-armed, U-shaped gonad that connects to the vulva at the midbody. The outgrowth of each gonad arm from the somatic gonad primordium is led by two female Distal Tip Cells (fDTC), while the Anchor Cell (AC) remains stationary and central to coordinate uterine and vulval development. The bHLH protein HLH-2 and its dimerization partners LIN-32 and HLH-12 had previously been shown to be required for fDTC specification. Here, we show that ectopic expression of both HLH-12 and LIN-32 in cells with AC potential transiently transforms them into fDTC-like cells. Furthermore, hlh-12 was known to be required for the fDTCs to sustain gonad arm outgrowth. Here, we show that ectopic expression of HLH-12 in the normally stationary AC causes displacement from its normal position, and that displacement likely results from activation of the leader program of fDTCs because it requires genes necessary for gonad arm outgrowth. Thus, HLH-12 is both necessary and sufficient to promote gonadal regulatory cell migration. As differences in female gonadal morphology of different nematode species reflect differences in the fate or migratory properties of the fDTCs or of the AC, we hypothesized that evolutionary changes in the expression of hlh-12 may underlie evolution of such morphological diversity. However, we were unable to identify an hlh-12 ortholog outside of Caenorhabditis. Instead, by performing a comprehensive phylogenetic analysis of all Class II bHLH proteins in multiple nematode species, we found that HLH-12 evolved within the Caenorhabditis clade, possibly by duplicative transposition of hlh-10. Our analysis suggests that control of gene regulatory hierarchies for gonadogenesis can be remarkably plastic during evolution without adverse phenotypic consequence.

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Mutations that Affect Channel Opening of Innexin Hemichannels in the C. elegans Gonad

10.20944/preprints202011.0151.v1 ◽

2020 ◽

Author(s):

Todd Starich ◽

David Greenstein

Keyword(s):

Cell Proliferation ◽

Gap Junctions ◽

Germ Cell ◽

Structural Model ◽

Loss Of Function ◽

C Elegans ◽

Somatic Gonad ◽

Channel Opening ◽

Germline Proliferation ◽

Germ Cell Proliferation

In C. elegans, gap junctions couple cells of the somatic gonad with the germline to support germ cell proliferation and gametogenesis. We previously characterized a strong loss-of-function mutation (T239I) affecting the second extracellular loop (EL2) of the somatic INX-8 hemichannel subunit. These mutant hemichannels form non-functional gap junctions with germline-expressed innexins. Here we describe the characterization of mutations that restore germ cell proliferation in the T239I EL2 mutant background. We recovered seven intragenic mutations located in diverse domains of INX-8 but not the EL domains. These second-site mutations compensate for the original channel defect to varying degrees, from nearly complete wild-type rescue, to partial rescue of germline proliferation. One suppressor mutation (E350K) supports the innexin cryo-EM structural model that the channel pore opening is surrounded by a cytoplasmic dome. Two suppressor mutations (S9L and I36N) may form leaky hemichannels that support germline proliferation but cause the demise of somatic sheath cells. Phenotypic analyses of three other suppressors reveal an equivalency in the rescue of germline proliferation and comparable delays in gametogenesis but a graded rescue of fertility. These latter mutations may be useful to probe interactions with the biochemical pathways that produce the molecules transiting through soma-germline gap junctions.

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The mab-21 gene of Caenorhabditis elegans encodes a novel protein required for choice of alternate cell fates

Development ◽

10.1242/dev.121.11.3615 ◽

1995 ◽

Vol 121 (11) ◽

pp. 3615-3626 ◽

Cited By ~ 9

Author(s):

K.L. Chow ◽

D.H. Hall ◽

S.W. Emmons

Keyword(s):

Cell Fate ◽

Hox Genes ◽

Cell Signalling ◽

Gene Mutations ◽

Genetic Modifiers ◽

Tail Region ◽

Cell Fates ◽

C Elegans ◽

Body Regions ◽

Novel Protein

The gene mab-21, which encodes a novel protein of 386 amino acids, is required for the choice of alternate cell fates by several cells in the C. elegans male tail. Three cells descended from the ray 6 precursor cell adopt fates of anterior homologs, and a fourth, lineally unrelated hypodermal cell is transformed into a neuroblast. The affected cells lie together in the lateral tail epidermis, suggesting that mab-21 acts as part of a short-range pattern-formation mechanism. Each of the changes in cell fate brought about by mab-21 mutants can be interpreted as a posterior-to-anterior homeotic transformation. mab-21 mutant males and hermaphrodites have additional pleiotropic phenotypes affecting movement, body shape and fecundity, indicating that mab-21 has functions outside the tail region of males. We show that the three known alleles of mab-21 are hypomorphs of a new gene. Mosaic analysis revealed that mab-21 acts cell autonomously to specify the properties of the sensory ray, but non-autonomously in the hypodermal versus neuroblast cell fate choice. Presence of cell signalling in the choice of the neuroblast fate was confirmed by cell ablation experiments. Mutations in mab-21 were shown previously to be genetic modifiers of the effects of HOM-C/Hox gene mutations on ray identity specification. The results presented here support the conclusion that mab-21 acts as part of a mechanism required for correct cell fate choice, possibly involving the function of HOM-C/Hox genes in several body regions.

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A normally attractive cell interaction is repulsive in two C. elegans mesodermal cell migration mutants

Development ◽

10.1242/dev.113.3.797 ◽

1991 ◽

Vol 113 (3) ◽

pp. 797-803 ◽

Cited By ~ 4

Author(s):

M.J. Stern ◽

H.R. Horvitz

Keyword(s):

Cell Migration ◽

Caenorhabditis Elegans ◽

Premature Termination ◽

Cell Interaction ◽

Egg Laying ◽

Wild Type ◽

Mesodermal Cell ◽

C Elegans ◽

Somatic Gonad ◽

Sex Myoblasts

In wild-type Caenorhabditis elegans hermaphrodites, two bilaterally symmetric sex myoblasts (SMs) migrate anteriorly to flank the precise center of the gonad, where they divide to generate the muscles required for egg laying (J. E. Sulston and H. R. Horvitz (1977) Devl Biol. 56, 110–156). Although this migration is largely independent of the gonad, a signal from the gonad attracts the SMs to their precise final positions (J. H. Thomas, M. J. Stern and H. R. Horvitz (1990) Cell 62, 1041–1052). Here we show that mutations in either of two genes, egl-15 and egl-17, cause the premature termination of the migrations of the SMs. This incomplete migration is caused by the repulsion of the SMs by the same cells in the somatic gonad that are the source of the attractive signal in wild-type animals.

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Patterning of the C. elegans 1 degrees vulval lineage by RAS and Wnt pathways

Development ◽

10.1242/dev.127.23.5047 ◽

2000 ◽

Vol 127 (23) ◽

pp. 5047-5058 ◽

Cited By ~ 2

Author(s):

M. Wang ◽

P.W. Sternberg

Keyword(s):

Short Range ◽

Precursor Cell ◽

Ras Signaling ◽

Cell Fates ◽

C Elegans ◽

Asymmetric Divisions ◽

Anchor Cell ◽

Wnt Pathways ◽

Vulval Precursor Cell ◽

Proper Orientation

In C. elegans, the descendants of the 1 degrees vulval precursor cell (VPC) establish a fixed spatial pattern of two different cell fates: E-F-F-E. The two inner granddaughters attach to the somatic gonadal anchor cell (AC) and generate four vulF cells, while the two outer granddaughters produce four vulE progeny. zmp-1::GFP, a molecular marker that distinguishes these two fates, is expressed in vulE cells, but not vulF cells. We demonstrate that a short-range AC signal is required to ensure that the pattern of vulE and vulF fates is properly established. In addition, signaling between the inner and outer 1 degrees VPC descendants, as well as intrinsic polarity of the 1 degrees VPC daughters, is involved in the asymmetric divisions of the 1 degrees VPC daughters and the proper orientation of the outcome. Finally, we provide evidence that RAS signaling is used during this new AC signaling event, while the Wnt receptor LIN-17 appears to mediate signaling between the inner and outer 1 degrees VPC descendants.

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