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Bioessays,
2006]
The endomesoderm gene regulatory network (GRN) of C. elegans is a rich resource for studying the properties of cell-fate-specification pathways. This GRN contains both cell-autonomous and cell non-autonomous mechanisms, includes network motifs found in other GRNs, and ties maternal factors to terminal differentiation genes through a regulatory cascade. In most cases, upstream regulators and their direct downstream targets are known. With the availability of resources to study close and distant relatives of C. elegans, the molecular evolution of this network can now be examined. Within Caenorhabditis, components of the endomesoderm GRN are well conserved. A cursory examination of the preliminary genome sequences of two parasitic nematodes, Haemonchus contortus and Brugia malayi, suggests that evolution in this GRN is occurring most rapidly for the zygotic genes that specify blastomere identity. BioEssays 28: 1010-1022, 2006. (c) 2006 Wiley Periodicals, Inc.
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Dev Dyn,
2010]
Cell specification requires that particular subsets of cells adopt unique expression patterns that ultimately define the fates of their descendants. In C. elegans, cell fate specification involves the combinatorial action of multiple signals that produce activation of a small number of "blastomere specification" factors. These initiate expression of gene regulatory networks that drive development forward, leading to activation of "tissue specification" factors. In this review, the C. elegans embryo is considered as a model system for studies of cell specification. The techniques used to study cell fate in this species, and the themes that have emerged, are described.
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Mol Reprod Dev,
2015]
Developmental robustness is the ability of an embryo to develop normally despite many sources of variation, from differences in the environment to stochastic cell-to-cell differences in gene expression. The nematode Caenorhabditis elegans exhibits an additional level of robustness: Unlike most other animals, the embryonic pattern of cell divisions is nearly identical from animal to animal. The endoderm (gut) lineage is an ideal model for studying such robustness as the juvenile gut has a simple anatomy, consisting of 20 cells that are derived from a single cell, E, and the gene regulatory network that controls E specification shares features with developmental regulatory networks in many other systems, including genetic redundancy, parallel pathways, and feed-forward loops. Early studies were initially concerned with identifying the genes in the network, whereas recent work has focused on understanding how the endoderm produces a robust developmental output in the face of many sources of variation. Genetic control exists at three levels of endoderm development: Progenitor specification, cell divisions within the developing gut, and maintenance of gut differentiation. Recent findings show that specification genes regulate all three of these aspects of gut development, and that mutant embryos can experience a "partial" specification state in which some, but not all, E descendants adopt a gut fate. Ongoing studies using newer quantitative and genome-wide methods promise further insights into how developmental gene-regulatory networks buffer variation. Mol. Reprod. Dev. 2015. 2015 Wiley Periodicals, Inc.
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Semin Cell Dev Biol,
2017]
The midgut (intestine) of the nematode, C. elegans, is a tube consisting of 20 cells that arises from a single embryonic precursor. Owing to its comparatively simple anatomy and the advantages inherent to the C. elegans system, the gut has been used as a model for organogenesis for more than 25 years. In this review, the salient features of C. elegans gut development are described from the E progenitor through to the 20-cell intestine. The core gene regulatory network that drives specification of the gut, and other genes with roles in organogenesis, lumen morphogenesis and the cell cycle, are also described. Questions for future work are posed.
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Biochim Biophys Acta,
2009]
The specification of the Caenorhabditis elegans endomesoderm has been the subject of study for more than 15 years. Specification of the 4-cell stage endomesoderm precursor, EMS, occurs as a result of the activation of a transcription factor cascade that starts with SKN-1, coupled with input from the Wnt/beta-catenin asymmetry pathway through the nuclear effector POP-1. As development proceeds, transiently-expressed cell fate factors are succeeded by stable, tissue/organ-specific regulators. The pathway is complex and uses motifs found in all transcriptional networks. Here, the regulators that function in the C. elegans endomesoderm network are described. An examination of the motifs in the network suggests how they may have evolved from simpler gene interactions. Flexibility in the network is evident from the multitude of parallel functions that have been identified and from apparent changes in parts of the corresponding network in Caenorhabditis briggsae. Overall, the complexities of C. elegans endomesoderm specification build a picture of a network that is robust, complex, and still evolving.
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Dev Biol,
2002]
The nematode Caenorhabditis elegans is a triploblastic ecdysozoan, which, although it contains too few cells during embryogenesis to create discernible germ "layers," deploys similar programs for germ layer differentiation used in animals with many more cells. The endoderm arises from a single progenitor, the E cell, and is selected from among three possible fates by a three-state combinatorial regulatory system involving intersecting cell-intrinsic and intercellular signals. The core gene regulatory cascade that drives endoderm development, extending from early maternal regulators to terminal differentiation genes, is characterized by activation of successive tiers of transcription factors, including a sequential cascade of redundant GATA transcription factors. Each tier is punctuated by a cell division, raising the possibility that intercession of one cell cycle round, or DNA replication, is required for activation of the next tier. The existence of each tier in the regulatory hierarchy is justified by the assignment of a unique task and each invariably performs at least two functions: to activate the regulators in the next tier and to perform one other activity distinct from that of the next tier. While the regulatory inputs that initiate endoderm development are highly divergent, they mobilize a gene regulatory network for endoderm development that appears to be common to all triploblastic metazoans. Genome-wide functional genomic approaches, including identification of >800 transcripts that exhibit the same regulatory patterns as a number of endoderm-specific genes, are contributing to elucidation of the complete endoderm gene regulatory network in C. elegans. Dissection of the architecture of the C. elegans endoderm network may provide insights into the evolutionary plasticity and origins of this germ layer.