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1.
Tube formation is a widespread process during organogenesis. Specific cellular behaviors participate in the invagination of epithelial monolayers that form tubes. However, little is known about the evolutionary mechanisms of cell assembly into tubes during development. In Caenorhabditis elegans, the detailed step-to-step process of vulva formation has been studied in wild type and in several mutants. Here we show that cellular processes during vulva development, which involve toroidal cell formation and stacking of rings, are conserved between C. elegans and Pristionchus pacificus, two species of nematodes that diverged approximately 100 million years ago. These cellular behaviors are divided into phases of cell proliferation, short-range migration, and cell fusion that are temporally distinct in C. elegans but not in P. pacificus. Thus, we identify heterochronic changes in the cellular events of vulva development between these two species. We find that alterations in the division axes of two equivalent vulval cells from Left-Right cleavage in C. elegans to Anterior-Posterior division in P. pacificus can cause the formation of an additional eighth ring. Thus, orthogonal changes in cell division axes with alterations in the number and sequence of cell fusion events result in dramatic differences in vulval shape and in the number of rings in the species studied. Our characterization of vulva formation in P. pacificus compared to C. elegans provides an evolutionary-developmental foundation for molecular genetic analyses of organogenesis in different species within the phylum Nematoda. 相似文献
2.
Ras is required for a limited number of cell fates and not for general proliferation in Caenorhabditis elegans. 总被引:3,自引:0,他引:3
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Experiments with mammalian tissue culture cells have implicated the small GTPase Ras in the control of cellular proliferation. Evidence is presented here that this is not the case for a living animal, the nematode Caenorhabditis elegans: proliferation late in embryogenesis and throughout the four larval stages is not noticeably affected in animals lacking Ras in various parts of their cell lineages. Instead, genetic mosaic analysis of the let-60 gene suggests that Ras is required only, at least later in development (a maternal effect cannot be excluded), for establishment of a few temporally and spatially distinct cell fates. Only one of these, the duct cell fate, appears to be essential for viability. 相似文献
3.
S W Emmons 《BioEssays : news and reviews in molecular, cellular and developmental biology》1992,14(5):309-316
The C. elegans male tail is being studied as a model to understand how genes specify the form of multicellular animals. Morphogenesis of the specialized male copulatory organ takes place in the last larval stages during male development. Genetic analysis is facilitated because the structure is not necessary for male viability or for strain propagation. Analysis of developmental mutants, isolated in several functional and morphological screens, has begun to reveal how fates of cells are determined in the cell lineages, and how the specification of cell fates affects the morphology of the structure. Cytological studies in wild type and in mutants have been used to study the mechanism of pattern formation in the tail peripheral nervous system. The ultimate goal is to define the entire pathway leading to the male copulatory organ. 相似文献
4.
Ambros V 《Development (Cambridge, England)》1999,126(9):1947-1956
In Caenorhabditis elegans, the fates of the six multipotent vulva precursor cells (VPCs) are specified by extracellular signals. One VPC expresses the primary (1 degrees ) fate in response to a Ras-mediated inductive signal from the gonad. The two VPCs flanking the 1 degrees cell each express secondary (2 degrees ) fates in response to lin-12-mediated lateral signaling. The remaining three VPCs each adopt the non-vulval tertiary (3 degrees ) fate. Here I describe experiments examining how the selection of these vulval fates is affected by cell cycle arrest and cell cycle-restricted lin-12 activity. The results suggest that lin-12 participates in two developmental decisions separable by cell cycle phase: lin-12 must act prior to the end of VPC S phase to influence a 1 degrees versus 2 degrees cell fate choice, but must act after VPC S phase to influence a 3 degrees versus 2 degrees cell fate choice. Coupling developmental decisions to cell cycle transitions may provide a mechanism for prioritizing or ordering choices of cell fates for multipotential cells. 相似文献
5.
The Caenorhabditis elegans PcG-like gene sop-2 regulates the temporal and sexual specificities of cell fates
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How spatial, temporal, and sexual specific cues are integrated to specify distinct cell fates during multicellular organism development is largely unknown. Here we demonstrate that the Caenorhabditis elegans PcG-like gene sop-2 determines the temporal and sexual specificities of a row of hypodermal seam cells, in addition to specifying their positional identities. Loss-of-function of sop-2 causes premature expression of adult fates at larval stages. sop-2 acts upstream of lin-29 in the heterochronic pathway and genetically interacts with other heterochronic genes in specifying the temporal fates of seam cells at different larval stages. We show that the number of ALG-1-containing P bodies is increased in seam cells in sop-2 mutants. Furthermore, the microRNA-mediated repression of a heterochronic gene reporter is enhanced in sop-2 mutants. Mutations in sop-2 also cause partial hermaphrodite-to-male sexual transformations. The homeotic transformations, heterochronic defects, and sexual transformations can occur concomitantly in sop-2 mutants. In summary, our studies reveal that sop-2 integrates spatial, temporal, and sexual cues during C. elegans development. 相似文献
6.
Cell invasion is a tightly controlled process occurring during development and tumor progression. The nematode Caenorhabditis elegans serves as a genetic model to study cell invasion during normal development. In the third larval stage, the anchor cell in the somatic gonad first induces and then invades the adjacent epidermal vulval precursor cells. The homolog of the Evi-1 oncogene, egl-43, is necessary for basement membrane destruction and anchor cell invasion. egl-43 is part of a regulatory network mediating cell invasion downstream of the fos-1 proto-oncogene. In addition, EGL-43 is required to specify the cell fates of ventral uterus cells downstream of or in parallel with LIN-12 NOTCH. Comparison with mammalian Evi-1 suggests a conserved pathway controlling cell invasion and cell fate specification. 相似文献
7.
The protein kinase Raf is an important signaling protein. Raf activation is initiated by an interaction with GTP-bound Ras, and Raf functions in signal transmission by phosphorylating and activating a mitogen-activated protein (MAP) kinase kinase named MEK. We identified 13 mutations in the Caenorhabditis elegans lin-45 raf gene by screening for hermaphrodites with abnormal vulval formation or germline function. Weak, intermediate, and strong loss-of-function or null mutations were isolated. The phenotype caused by the most severe mutations demonstrates that lin-45 is essential for larval viability, fertility, and the induction of vulval cell fates. The lin-45(null) phenotype is similar to the mek-2(null) and mpk-1(null) phenotypes, indicating that LIN-45, MEK-2, and MPK-1 ERK MAP kinase function in a predominantly linear signaling pathway. The lin-45 alleles include three missense mutations that affect the Ras-binding domain, three missense mutations that affect the protein kinase domain, two missense mutations that affect the C-terminal 14-3-3 binding domain, three nonsense mutations, and one small deletion. The analysis of the missense mutations indicates that Ras binding, 14-3-3-binding, and protein kinase activity are necessary for full Raf function and suggests that a 14-3-3 protein positively regulates Raf-mediated signaling during C. elegans development. 相似文献
8.
Kim HS Murakami R Quintin S Mori M Ohkura K Tamai KK Labouesse M Sakamoto H Nishiwaki K 《Development (Cambridge, England)》2011,138(18):4013-4023
Cytoskeletal regulation is important in cell migration. The Caenorhabditis elegans gonadal distal tip cells (DTCs) offer a simple model with which to investigate the mechanism of cell migration in organogenesis. Here, we report that one of the spectraplakin isoforms, VAB-10B1, plays an essential role in cell and nuclear migration of DTCs by regulating the actin and microtubule (MT) cytoskeleton. In the vab-10(tk27) mutant, which lacks VAB-10B1, alignment of filamentous (F)-actin and MTs was weakly and severely disorganized, respectively, which resulted in a failure to translocate the DTC nucleus and a premature termination of DTC migration. An MT growing-tip marker, EBP-2-GFP, revealed that polarized outgrowth of MTs towards the nuclei of migrating DTCs was strikingly impaired in tk27 animals. A vab-10 mini-gene encoding only the actin- and MT-binding domains significantly rescued the gonadal defects, suggesting that VAB-10B1 has a role in linking actin and MT filaments. These results suggest that VAB-10B1/spectraplakin regulates the polarized alignment of MTs, possibly by linking F-actin and MTs, which enables normal nuclear translocation and cell migration of DTCs. 相似文献
9.
10.
D J Montell 《Development (Cambridge, England)》1999,126(14):3035-3046
Cell migrations are found throughout the animal kingdom and are among the most dramatic and complex of cellular behaviors. Historically, the mechanics of cell migration have been studied primarily in vitro, where cells can be readily viewed and manipulated. However, genetic approaches in relatively simple model organisms are yielding additional insights into the molecular mechanisms underlying cell movements and their regulation during development. This review will focus on these simple model systems where we understand some of the signaling and receptor molecules that stimulate and guide cell movements. The chemotactic guidance factor encoded by the Caenorhabditis elegans unc-6 locus, whose mammalian homolog is Netrin, is perhaps the best known of the cell migration guidance factors. In addition, receptor tyrosine kinases (RTKs), and FGF receptors in particular, have emerged as key mediators of cell migration in vivo, confirming the importance of molecules that were initially identified and studied in cell culture. Somewhat surprisingly, screens for mutations that affect primordial germ cell migration in Drosophila have revealed that enzymes involved in lipid metabolism play a role in guiding cell migration in vivo, possibly by producing and/or degrading lipid chemoattractants or chemorepellents. Cell adhesion molecules, such as integrins, have been extensively characterized with respect to their contribution to cell migration in vitro and genetic evidence now supports a role for these receptors in certain instances in vivo as well. The role for non-muscle myosin in cell motility was controversial, but has now been demonstrated genetically, at least in some cell types. Currently the best characterized link between membrane receptor signaling and regulation of the actin cytoskeleton is that provided by the Rho family of small GTPases. Members of this family are clearly essential for the migrations of some cells; however, key questions remain concerning how chemoattractant and chemorepellent signals are integrated within the cell and transduced to the cytoskeleton to produce directed cell migration. New types of genetic screens promise to fill in some of these gaps in the near future. 相似文献
11.
In C. elegans, the first embryonic axis is established shortly after fertilization and requires both the microtubule and microfilament cytoskeleton. Cues from sperm-donated centrosomes result in a cascade of events that polarize the distribution of widely conserved PAR proteins at the cell cortex. The PAR proteins in turn polarize the cytoplasm and position mitotic spindles. Lessons learned from C. elegans should improve our understanding of how cells become polarized and divide asymmetrically during development. 相似文献
12.
Prodomain-dependent tissue targeting of an ADAMTS protease controls cell migration in Caenorhabditis elegans
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Members of the ADAMTS (a disintegrin and metalloprotease with thrombospondin motifs) family of secreted proteins play important roles in animal development and pathogenesis. However, the lack of in vivo models has hampered elucidation of the mechanisms by which these enzymes are recruited to specific target tissues and the timing of their activation during development. Using transgenic worms and primary cell cultures, here we show that MIG-17, an ADAMTS family protein required for gonadal leader cell migration in Caenorhabditis elegans, is recruited to the gonadal basement membrane in a prodomain-dependent manner. The activation of MIG-17 to control leader cell migration requires prodomain removal, which is suggested to occur autocatalytically in vitro. Although the prodomains of ADAMTS proteases have been implicated in maintaining enzymatic latency, polypeptide folding and secretion, our findings demonstrate that the prodomain has an unexpected function in tissue-specific targeting of MIG-17; this prodomain targeting function may be shared by other ADAMTSs including those in vertebrates. 相似文献
13.
The activation of ADAMTS (a disintegrin and metalloprotease with thrombospondin motifs) family proteases depends on removal of the prodomain. Although several studies suggest that ADAMTS activities play roles in development, homeostasis and disease, it remains unclear when and where the enzymes are activated in vivo. MIG-17, a Caenorhabditis elegans glycoprotein belonging to the ADAMTS family, is secreted from the body wall muscle cells and localizes to the gonadal basement membrane to control the migration of gonadal distal tip cells. Here, we developed a monoclonal antibody that recognizes the N-terminal neo-epitope of the activated MIG-17. In western blotting, the antibody specifically detected the activated form, the signal for which dramatically increased during the third and fourth larval stages, when MIG-17 is required to direct distal tip cell migration. In in situ staining, the monoclonal antibody recognized the activated form in the basement membrane, whereas it failed to detect a processing-resistant mutant form localized to the basement membrane. MIG-17 was activated in the basement membranes of the muscle, intestine and gonad in the third larval stage, and downregulated in nongonadal basement membranes in young adults and in gonadal basement membranes in older adults. Thus, the activation of MIG-17 is regulated in a spatiotemporal manner during C. elegans development. This is the first report demonstrating the regulated activation of an ADAMTS protein in vivo. Our results suggest that monoclonal antibodies against neo-epitopes have potential as powerful tools for detecting activation of ADAMTSs during development and in disease pathogenesis. 相似文献
14.
The number of nongonadal nuclei in the free-living soil nematode Caenorhabditis elegans increases from about 550 in the newly hatched larva to about 810 in the mature hermaphrodite and to about 970 in the mature male. The pattern of cell divisions which leads to this increase is essentially invariant among individuals; rigidly determined cell lineages generate a fixed number of progeny cells of strictly specified fates. These lineages range in length from one to eight sequential divisions and lead to significant developmental changes in the neuronal, muscular, hypodermal, and digestive systems. Frequently, several blast cells follow the same asymmetric program of divisions; lineally equivalent progeny of such cells generally differentiate into functionally equivalent cells. We have determined these cell lineages by direct observation of the divisions, migrations, and deaths of individual cells in living nematodes. Many of the cell lineages are involved in sexual maturation. At hatching, the hermaphrodite and male are almost identical morphologically; by the adult stage, gross anatomical differences are obvious. Some of these sexual differences arise from blast cells whose division patterns are initially identical in the male and in the hermaphrodite but later diverge. In the hermaphrodite, these cells produce structures used in egg-laying and mating, whereas, in the male, they produce morphologically different structures which function before and during copulation. In addition, development of the male involves a number of lineages derived from cells which do not divide in the hermaphrodite. Similar postembryonic developmental events occur in other nematode species. 相似文献
15.
16.
Vulval epithelial tubes invaginate through concerted cell migration, ring formation, stacking of rings and intra-ring cell fusion in the nematodes Caenorhabditis elegans, Oscheius tipulae and Pristionchus pacificus. The number of rings forming the invaginations is invariantly seven, six, and eight, respectively. We hypothesize that each ring is formed from pairs of symmetrically positioned primordial vulval cells following three premises: If the final cell division is left-right, the daughters will fuse, migrate and form only one ring. If these cells do not divide, one ring will form. If the final division is anterior-posterior, two rings will form. We test the ring hypothesis and found coincidence between the patterns of vulva cell divisions and the number of rings for 12 species. We find heterochronic variations in the timing of division, migration and fusion of the vulval cells between species. We report a unique ring-independent pathway of vulva formation in Panagrellus redivivus. C. elegans lin-11(n389) mutation results in cell fate transformations including changes in the orientation of vulval cell division. lin-11 animals have an additional ring, as predicted by the ring hypothesis. We propose that the genetic pathway determining how vulval cells invaginate evolves through ring-dependent and ring-independent mechanisms. 相似文献
17.
The Caenorhabditis elegans distal tip cells (DTCs) are an in vivo model for the study of developmentally regulated cell migration. In this study, we characterize a novel role for CCDC-55, a conserved coiled-coil domain containing protein, in DTC migration and larval development in C. elegans. Although animals homozygous for a probable null allele, ccdc-55(ok2851), display an early larval arrest, RNAi depletion experiments allow the analysis of later phenotypes and suggest that CCDC-55 is needed within the DTC for migration to cease at the end of larval morphogenesis. The ccdc-55 gene is found in an operon with rnf-121 and rnf-5, E3 ubiquitin ligases that target cell migration genes such as the β-integrin PAT-3. Genetic interaction studies using RNAi depletion and the deletion alleles rnf-121(ok848) and rnf-5(tm794) indicate that CCDC-55 and the RNF genes act at least partially in parallel to promote termination of cell migration in the adult DTC. 相似文献
18.
The powerful genetics, genomics and microscopy tools available for C. elegans make it well suited to studying how epithelial cells adhere to one another and the extracellular matrix, and how the integrated, simultaneous activities of multiple cell adhesion complexes function to shape an organism. Recent studies using forward and reverse genetics have shed light on how phylogenetically conserved cell adhesion complexes, such as the cadherin/catenin complex, claudins, the Discs large complex and hemidesmosome-like attachment structures, regulate epithelial cell adhesion, providing new insights into conserved cell adhesion mechanisms in higher eukaryotes. 相似文献
19.
The Drosophila tracheal system is a network of epithelial tubes that arises from the tracheal placodes, lateral clusters of ectodermal cells
in ten embryonic segments. The cells of each cluster invaginate and subsequent formation of the tracheal tree occurs by cell
migration and fusion of tracheal branches, without cell division. The combined action of the Decapentaplegic (Dpp), Epidermal
growth factor (EGF) and breathless/branchless pathways are thought to be responsible for the pattern of tracheal branches.
We ask how these transduction pathways regulate cell migration and we analyse the consequences on cell behaviour of the Dpp
and EGF pathways. We find that rhomboid (rho) mutant embryos display defects not only in tracheal cell migration but also in tracheal cell invagination unveiling a new
role for EGF signalling in the formation of the tracheal system. These results indicate that the transduction pathways that
control tracheal cell migration are active in different steps of tracheal formation, beginning at invagination. We discuss
how the consecutive steps of tracheal morphogenesis might affect the final branching pattern.
Received: 9 October 1998 / Accepted: 5 November 1998 相似文献
20.
Cadherins are one of the major families of adhesion molecules with diverse functions during embryonic development. Fat-like cadherins form an evolutionarily conserved subgroup characterized by an unusually large number of cadherin repeats in the extracellular domain. Here we describe the role of the Fat-like cadherin CDH-4 in Caenorhabditis elegans development. Cdh-4 mutants are characterized by hypodermal defects leading to incompletely penetrant embryonic or larval lethality with variable morphogenetic defects. Independently of the morphogenetic defects cdh-4 mutant animals also exhibit fasciculation defects in the ventral and dorsal cord, the major longitudinal axon tracts, as well as migration defects of the Q neuroblasts. In addition CDH-4 is essential for establishing and maintaining the attachment between the buccal cavity and the pharynx. Cdh-4 is expressed widely in most affected cells and tissues during embryogenesis suggesting that CDH-4 functions to ensure that proper cell contacts are made and maintained during development. 相似文献