pop-1/TCF, ref-2/ZIC and T-box factors regulate the development of anterior cells in the C. elegans embryo

Rumley, Jonathan D.; Preston, Elicia; Cook, Dylan; Peng, Felicia; Zacharias, Amanda L.; Wu, Lucy; Jileaeva, Ilona; Murray, John I.

doi:10.1016/j.ydbio.2022.05.019

Cited by 2 publications

References 78 publications

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Mechanisms of lineage specification in Caenorhabditis elegans

Liu,

Murray

2023

Genetics

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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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Mechanisms of lineage specification in Caenorhabditis elegans

Liu,

Murray

2023

Genetics

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Abnormal behavior is reversible in a chromatin mutant

Rodriguez,

Reeves,

Wang

et al. 2023

Preprint

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Many human neurodevelopmental disorders are caused byde novomutations in histone modifying enzymes. These patients have craniofacial defects, developmental delay, intellectual disability and behavioral abnormalities, but it remains unclear how the mutations lead to such developmental defects. Here we take advantage of the invariantC. eleganslineage along with a unique double mutant in the H3K4me1/2 demethylase SPR-5/LSD1/KDM1A and the H3K9 methyltransferase MET-2/SETDB1 to address this question. We demonstrate thatspr-5; met-2double mutant worms have a severe chemotaxis defect that is dependent upon the ectopic expression of germline genes in somatic tissues. In addition, by performing single-cell RNAseq, we find that germline genes begin to be ectopically expression widely inspr-5; met-2embryos. However, surprisingly we found thatspr-5; met-2mutants have no somatic lineage defects prior to the 200-cell stage of embryogenesis. This suggests that the altered chemotaxis behavior may be due to ongoing defect in terminally differentiated cells rather than a defect in development. To test this directly, we used RNAi to shut off the ectopic expression of germline genes in L2spr-5; met-2larvae, which have a fully formed nervous system. Remarkably, we find that shutting off the ectopic germline expression rescues normal chemotaxis behavior in the same adult worms that previously had a chemotaxis defect at the L2 stage. This suggests that ongoing ectopic transcription can block normal behavior in a fully intact nervous system. These data raise the possibility that intellectual disability and altered behavior in neurodevelopmental syndromes, caused by mutations in histone modifying enzymes, could be due to ongoing ectopic transcription and may be reversible.

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pop-1/TCF, ref-2/ZIC and T-box factors regulate the development of anterior cells in the C. elegans embryo

Cited by 2 publications

References 78 publications

Mechanisms of lineage specification in Caenorhabditis elegans

Mechanisms of lineage specification in Caenorhabditis elegans

Abnormal behavior is reversible in a chromatin mutant

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