Susan E. Mango (2007) WormBook "The C. elegans pharynx: a model for organogenesis."

Susan E. Mango

[WormBook, 2007]

The C. elegans foregut (pharynx) has emerged as a powerful system to study organ formation during embryogenesis. Here I review recent advances regarding cell-fate specification and epithelial morphogenesis during pharynx development. Maternally-supplied gene products function prior to gastrulation to establish pluripotent blastomeres. As gastrulation gets under way, pharyngeal precursors become committed to pharyngeal fate in a process that requires PHA-4 /FoxA and the Tbox transcription factors TBX-2 , TBX-35 , TBX-37 and TBX-38 . Subsequent waves of gene expression depend on the affinity of PHA-4 for its target promoters, coupled with combinatorial strategies such as feed-forward and positive-feedback loops. During later embryogenesis, pharyngeal precursors undergo reorganization and a mesenchymal-to-epithelial transition to form the linear gut tube. Surprisingly, epithelium formation does not depend on cadherins, catenins or integrins. Rather, the kinesin ZEN-4 /MKLP1 and CYK-4 /RhoGAP are critical to establish the apical domain during epithelial polarization. Finally, I discuss similarities and differences between the nematode pharynx and the vertebrate heart.

Monica C. Vella et al. (2005) WormBook "C. elegans microRNAs."

Monica C. Vella, Frank J. Slack

[WormBook, 2005]

MicroRNAs (miRNAs) are small, non-coding regulatory RNAs found in many phyla that control such diverse events as development, metabolism, cell fate and cell death. They have also been implicated in human cancers. The C. elegans genome encodes hundreds of miRNAs, including the founding members of the miRNA family lin-4 and let-7 . Despite the abundance of C. elegans miRNAs, few miRNA targets are known and little is known about the mechanism by which they function. However, C. elegans research continues to push the boundaries of discovery in this area. lin-4 and let-7 are the best understood miRNAs. They control the timing of adult cell fate determination in hypodermal cells by binding to partially complementary sites in the mRNA of key developmental regulators to repress protein expression. For example, lin-4 is predicted to bind to seven sites in the lin-14 3'' untranslated region (UTR) to repress LIN-14 , while let-7 is predicted to bind two let-7 complementary sites in the lin-41 3'' UTR to down-regulate LIN-41 . Two other miRNAs, lsy-6 and mir-273 , control left-right asymmetry in neural development, and also target key developmental regulators for repression. Approximately one third of the C. elegans miRNAs are differentially expressed during development indicating a major role for miRNAs in C. elegans development. Given the remarkable conservation of developmental mechanism across phylogeny, many of the principles of miRNAs discovered in C. elegans are likely to be applicable to higher animals.

Cathy Savage-Dunn (2005) WormBook "TGF-beta signaling."

Cathy Savage-Dunn

[WormBook, 2005]

TGF-beta superfamily ligands play fundamental roles in the development and physiology of diverse animal species. Genetic and genomic analyses in the model organism Caenorhabditis elegans have contributed to the understanding of TGF-beta -related signal transduction mechanisms. In this chapter, I describe the currently characterized TGF-beta -related signals and signal transduction cassettes in C. elegans. Homology searches of the genome identify five TGF-beta -related genes, for which functions have been identified for three. Two of the TGF-beta -related genes, daf-7 and dbl-1 , function through conventional signaling pathways. These signaling pathways are comprised of ser/thr kinase receptors, Smads, and transcription co-factors. A third TGF-beta -related gene, unc-129 , functions in axonal guidance using novel signaling mechanisms. Thus, TGF-beta -related signaling in C. elegans proceeds via both conserved and novel paradigms that can inform studies in other animal systems.

Gartner A et al. (2008) WormBook "Germline survival and apoptosis."

Boag PR, Gartner A, Blackwell TK

[WormBook, 2008]

Germline apoptosis shares with somatic apoptosis a reliance on key components of the core apoptotic machinery, including CED-3 and CED-4. However, germline apoptosis differs from somatic apoptosis in its regulation. Whereas somatic apoptosis is developmentally programmed by cell lineage, germline apoptosis occurs as part of an oogenesis program. One category of germline apoptosis, dubbed "physiological" germline apoptosis, reduces the number of cells that complete oogenesis, and is independent of the BH3-only apoptosis effecter EGL-1. A second category, termed "stress-induced" germline apoptosis, is triggered by a genomic integrity checkpoint. Some mechanisms that are monitored by this DNA-damage checkpoint are also involved in germ cell "immortality," or preservation of a continuous germ cell lineage over successive generations. In addition, exposure to certain environmental insults or pathogens induces germ cell apoptosis. Here we will review the mechanisms that control each of the pathways leading to germ cell apoptosis and discuss their functional significance. Germline apoptosis is an integral part of oogenesis in many animals, including humans. Because many of the regulators of C. elegans germline apoptosis are conserved, we suggest that this nematode provides a valuable model for understanding controls of germline apoptosis more broadly.

Barbara Conradt (2005) WormBook "Programmed cell death."

BARBARA CONRADT

[WormBook, 2005]

Programmed cell death is an integral component of C. elegans development. Genetic studies in C. elegans have led to the identification of more than two dozen genes that are important for the specification of which cells should live or die, the activation of the suicide program, and the dismantling and removal of dying cells. Molecular and biochemical studies have revealed the underlying conserved mechanisms that control these three phases of programmed cell death. In particular, an interplay of transcriptional regulatory cascades and networks involving CES-1 , CES-2 , HLH-1 / HLH-2 , TRA-1 , and other transcriptional regulators is crucial in activating the expression of the key death-inducing gene egl-1 in cells destined to die. A protein interaction cascade involving EGL-1 , CED-9 , CED-4 and CED-3 results in the activation of the key cell death protease CED-3 . The activation of CED-3 initiates the cell disassembly process and nuclear DNA fragmentation, which is mediated by the release of apoptogenic mitochondrial factors ( CPS-6 and WAH-1 ) and which involves multiple endo- and exo-nucleases such as NUC-1 and seven CRN nucleases. The recognition and removal of the dying cell is mediated by two partially redundant signaling pathways involving CED-1 , CED-6 and CED-7 in one pathway and CED-2 , CED-5 , CED-10 , CED-12 and PSR-1 in the other pathway. Further studies of programmed cell death in C. elegans will continue to advance our understanding of how programmed cell death is regulated, activated, and executed in multicellular organisms.