Mechano-logical model of C. elegans germ line suggests feedback on the cell cycle
2
Citation
1
Reference
10
Related Paper
Citation Trend
Abstract:
The Caenorhabditis elegans germ line is an outstanding model system in which to study the control of cell division and differentiation.Although many of the molecules that regulate germ cell proliferation and fate decisions have been identified, how these signals interact with cellular dynamics and physical forces within the gonad remains poorly understood.We therefore developed a dynamic, 3D in silico model of the C. elegans germ line, incorporating both the mechanical interactions between cells and the decision-making processes within cells.Our model successfully reproduces key features of the germ line during development and adulthood, including a reasonable ovulation rate, correct sperm count, and appropriate organization of the germ line into stably maintained zones.The model highlights a previously overlooked way in which germ cell pressure may influence gonadogenesis, and also predicts that adult germ cells might be subject to mechanical feedback on the cell cycle akin to contact inhibition.We provide experimental data consistent with the latter hypothesis.Finally, we present cell trajectories and ancestry recorded over the course of a simulation.The novel approaches and software described here link mechanics and cellular decisionmaking, and are applicable to modeling other developmental and stem cell systems.Keywords:
Cell fate determination
Germ line development
Cite
Citations (0)
Developmental Biology
Bombyx
Germ line development
Germ plasm
Cite
Citations (61)
Specification of the germline and its segregation from the soma mark one of the most crucial events in the lifetime of an organism. In different organisms, this specification can occur through either inheritance or inductive mechanisms. In species such as Xenopus and zebrafish, the specification of primordial germ cells relies on the inheritance of maternal germline determinants that are synthesized and sequestered in the germ plasm during oogenesis. In this review, we discuss the formation of the germ plasm, how germline determinants are recruited into the germ plasm during oogenesis, and the dynamics of the germ plasm during oogenesis and early embryonic development.
Germ plasm
Germ line development
Inheritance
Developmental Biology
Model Organism
Cite
Citations (2)
Special cytoplasm, called germ plasm, that is essential for the differentiation of germ cells is localized in a particular region of Caenorhabditis elegans, Drosophila and Xenopus eggs. The mode of founder cell formation of germline, the origin and behavior of the germline granules, and the molecules localized in germline cells are compared in these organisms. The common characteristics of the organisms are mainly as follows. First, the founder cells of germline are established before the intiation of gastrulation. Second, the germline granules or their derivatives are always present in germline cells or germ cells throughout the life cycle in embryos, larvae, and adults. Lastly, among the proteins localized in the germ plasm, only Vasa protein or its homolog is detected in the germline cells or germ cells throughout the life cycle. As the protein of vasa homolog has been reported to be also localized in the germline‐specific structure or nuage in some of the organisms without the germ plasm, the possibility that the mechanism for differentiation of primordial germ cells is basically common in all organisms with or without the germ plasm is discussed.
Germ plasm
Germ line development
Cite
Citations (138)
Abstract In Caenorhabditis elegans, germ granules called P granules are directly inherited from mother to daughter and segregate with the germ lineage as it separates from the soma during initial embryonic cell divisions. Here we define meg-1 and meg-2 (maternal-effect germ-cell defective), which are expressed in the maternal germline and encode proteins that localize exclusively to P granules during embryonic germline segregation. Localization of MEG-1 to P granules depends upon the membrane-bound protein MES-1. meg-1 mutants exhibit multiple germline defects: P-granule mis-segregation in embryos, underproliferation and aberrant P-granule morphology in larval germ cells, and ultimately, sterility as adults. The penetrance of meg-1 phenotypes increases when meg-2 is also absent. Loss of the P-granule component pgl-1 in meg-1 mutants increases germ-cell proliferation, while loss of glh-1 decreases proliferation. Because meg-1 is provided maternally but its action is required in the embryonic germ lineage during segregation from somatic lineages, it provides a critical link for ensuring the continuity of germline development from one generation to the next.
Granule (geology)
Cite
Citations (37)
Primordial germ cells (PGCs) are the stem cells of the germline. Generally, germline induction occurs via zygotic factors or the inheritance of maternal determinants called germ plasm (GP). GP is packaged into ribonucleoprotein complexes within oocytes and later promotes the germline fate in embryos. Once PGCs are specified by either mechanism, GP components localize to perinuclear granular-like structures. Although components of zebrafish PGC germ granules have been studied, the maternal factors regulating their assembly and contribution to germ cell development are unknown. Here, we show that the scaffold protein Dazap2 binds to Bucky ball, an essential regulator of oocyte polarity and GP assembly, and colocalizes with the GP in oocytes and in PGCs. Mutational analysis revealed a requirement for maternal Dazap2 (MDazap2) in germ-granule maintenance. Through molecular epistasis analyses, we show that MDazap2 is epistatic to Tdrd7 and maintains germ granules in the embryonic germline by counteracting Dynein activity.
Germ line development
Germ plasm
Cite
Citations (6)
All animals can be classified into three types depending on their modes of germ cell formation; epigenetic, intermediate and preformistic. In urodeles, which show the intermediate mode, primordial germ cells (PGCs) are morphologically recognized at first in early tailbud embryos. The PGCs, which are located within the lateral plate mesoderm, are induced as part of the regional induction of the mesoderm by the vegetal yolk endoderm. No cytologically distinctive, germ cell-specific germ plasma can be detected during early development of urodeles. 'Nuage' materials, which are specific to germ line cells in almost all animals, do, however, appear in the cytoplasm of the urodele PGCs during later embryogenesis. In contrast, PGCs in anurans are preformistically established under the influence of germ plasma. Because all germ cells, once established, show virtually identical behavior, regardless of whether different modes of germ cell formation are employed, the basic mechanism of germ cell formation and differentiation in all animals could be similar at the molecular levels. Although the molecules involved in germ cell formation in amphibians have not been identified, many aspects of germ plasm formation in anurans are similar to Drosophila, in which three classes of genes involved in germ cell formation have been identified: Class I genes are necessary for pattern specification during germ cell formation, Class II for the assembly of germ plasm components, and Class III for germ cell segregation. Assuming that germ cell formation in all animals requires the expression of all such genes, the three modes of germ cell formation mentioned above could be explained in terms of spatio-temporal expression of genes which are similar to those that have been identified in Drosophila. A tentative model of gene regulation for the three different modes of germ cell formation has been proposed in terms of temporal expression of these three classes of genes.
Germ plasm
Germ line development
Polarity in embryogenesis
Cite
Citations (27)
The starting point for this work was to use the hypodermal seam of C. elegans as a model system to study cell fate determination. Even though the seam is a relatively simple developmental system, the mechanisms that control cell fate determination in the seam lineages are connected in a highly complex regulatory network. This work has yielded novel insight into the links between the patterning mechanisms at work during the development of the C. elegans epidermal lineages. The study of these mechanisms in C. elegans is relevant because it may ultimately lead to a better understanding of the role of evolutionarily conserved developmental regulators, such as the COMPASS complex, in human diseases such as cancer.
Cell fate determination
Model Organism
Caenorhabditis
Compass
Developmental Biology
Cite
Citations (1)
Mammalian primordial germ cells (PGCs) are induced in the embryonic epiblast, before migrating to the nascent gonads. In fish, frogs, and birds, the germline segregates even earlier, through the action of maternally inherited germ plasm. Across vertebrates, migrating PGCs retain a broad developmental potential, regardless of whether they were induced or maternally segregated. In mammals, this potential is indicated by expression of pluripotency factors, and the ability to generate teratomas and pluripotent cell lines. How the germline loses this developmental potential remains unknown. Our genome-wide analyses of embryonic human and mouse germlines reveal a conserved transcriptional program, initiated in PGCs after gonadal colonization, that differentiates germ cells from their germline precursors and from somatic lineages. Through genetic studies in mice and pigs, we demonstrate that one such gonad-induced factor, the RNA-binding protein DAZL, is necessary in vivo to restrict the developmental potential of the germline; DAZL’s absence prolongs expression of a Nanog pluripotency reporter, facilitates derivation of pluripotent cell lines, and causes spontaneous gonadal teratomas. Based on these observations in humans, mice, and pigs, we propose that germ cells are determined after gonadal colonization in mammals. We suggest that germ cell determination was induced late in embryogenesis—after organogenesis has begun—in the common ancestor of all vertebrates, as in modern mammals, where this transition is induced by somatic cells of the gonad. We suggest that failure of this process of germ cell determination likely accounts for the origin of human testis cancer.
Germ line development
Germ plasm
Epiblast
Homeobox protein NANOG
Cite
Citations (98)