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Wiley Interdiscip Rev Dev Biol,
2018]
The convergence of developmental biology and modern genomics tools brings the potential for a comprehensive understanding of developmental systems. This is especially true for the Caenorhabditis elegans embryo because its small size, invariant developmental lineage, and powerful genetic and genomic tools provide the prospect of a cellular resolution understanding of messenger RNA (mRNA) expression and regulation across the organism. We describe here how a systems biology framework might allow large-scale determination of the embryonic regulatory relationships encoded in the C. elegans genome. This framework consists of two broad steps: (a) defining the "parts list"-all genes expressed in all cells at each time during development and (b) iterative steps of computational modeling and refinement of these models by experimental perturbation. Substantial progress has been made towards defining the parts list through imaging methods such as large-scale green fluorescent protein (GFP) reporter analysis. Imaging results are now being augmented by high-resolution transcriptome methods such as single-cell RNA sequencing, and it is likely the complete expression patterns of all genes across the embryo will be known within the next few years. In contrast, the modeling and perturbation experiments performed so far have focused largely on individual cell types or genes, and improved methods will be needed to expand them to the full genome and organism. This emerging comprehensive map of embryonic expression and regulatory function will provide a powerful resource for developmental biologists, and would also allow scientists to ask questions not accessible without a comprehensive picture. This article is categorized under: Invertebrate Organogenesis > Worms Technologies > Analysis of the Transcriptome Gene Expression and Transcriptional Hierarchies > Gene Networks and Genomics.
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Genetics,
2023]
The studies of cell fate and lineage specification are fundamental to our understanding of the development of multicellular organisms. Caenorhabditis elegans has been one of the premiere systems for studying cell fate specification mechanisms at single cell resolution, due to its transparent nature, the invariant cell lineage, and fixed number of somatic cells. We discuss the general themes and regulatory mechanisms that have emerged from these studies, with a focus on somatic lineages and cell fates. We next review the key factors and pathways that regulate the specification of discrete cells and lineages during embryogenesis and postembryonic development; we focus on transcription factors and include numerous lineage diagrams that depict the expression of key factors that specify embryonic founder cells and postembryonic blast cells, and the diverse somatic cell fates they generate. We end by discussing some future perspectives in cell and lineage specification.
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Genesis,
2016]
Understanding how a single cell, the zygote, can divide and differentiate to produce the diverse animal cell types is a central goal of developmental biology research. The model organism Caenorhabditis elegans provides a system that enables a truly comprehensive understanding of this process across all cells. Its invariant cell lineage makes it possible to identify all of the cells in each individual and compare them across organisms. Recently developed methods automate the process of cell identification, allowing high-throughput gene expression characterization and phenotyping at single cell resolution. In this Review, we summarize the sequences of events that pattern the lineage including establishment of founder cell identity, the signaling pathways that diversify embryonic fate, and the regulators involved in patterning within these founder lineages before cells adopt their terminal fates. We focus on insights that have emerged from automated approaches to lineage tracking, including insights into mechanisms of robustness, context-specific regulation of gene expression, and temporal coordination of differentiation. We suggest a model by which lineage history produces a combinatorial code of transcription factors that act, often redundantly, to ensure terminal fate. This article is protected by copyright. All rights reserved.
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Genome Res,
2005]
The Caenorhabditis elegans genome sequence is now complete, fully contiguous telomere to telomere and totaling 100,291,840 bp. The sequence has catalyzed the collection of systematic data sets and analyses, including a curated set of 19,735 protein-coding genes-with >90% directly supported by experimental evidence-and >1300 noncoding RNA genes. High-throughput efforts are under way to complete the gene sets, along with studies to characterize gene expression, function, and regulation on a genome-wide scale. The success of the worm project has had a profound effect on genome sequencing and on genomics more broadly. We now have a solid platform on which to build toward the lofty goal of a true molecular understanding of worm biology with all its implications including those for human health.