Metazoan development demands not only precise cell fate differentiation but also accurate timing of cell division to ensure proper development. How cell divisions are temporally coordinated during development is poorly understood. Caenorhabditis elegans embryogenesis provides an excellent opportunity to study this coordination due to its invariant development and widespread division asynchronies. One of the most pronounced asynchronies is a significant delay of cell division in two endoderm progenitor cells, Ea and Ep, hereafter referred to as E2, relative to its cousins that mainly develop into mesoderm organs and tissues. To unravel the genetic control over the endodermspecific E2 division timing, a total of 822 essential and conserved genes were knocked down using RNAi followed by quantification of cell cycle lengths using in toto imaging of C. elegans embryogenesis and automated lineage. Intriguingly, knockdown of numerous genes encoding the components of general transcription pathway or its regulatory factors leads to a significant reduction in the E2 cell cycle length but an increase in cell cycle length of the remaining cells, indicating a differential requirement of transcription for division timing between the two. Analysis of lineage-specific RNA-seq data demonstrates an earlier onset of transcription in endoderm than in other germ layers, the timing of which coincides with the birth of E2, supporting the notion that the endoderm-specific delay in E2 division timing demands robust zygotic transcription. The reduction in E2 cell cycle length is frequently associated with cell migration defect and gastrulation failure. The results suggest that a tissue-specific transcriptional activation is required to coordinate fate differentiation, division timing, and cell migration to ensure proper development.Proper development of metazoans depends not only on precise differentiation of cell fate but also on tight control over division timing or division pace between cells, which we refer to as temporal coordination. A normal fate specification without correct division timing may lead to catastrophes, for example, cancerous development (1). Therefore, metazoan development demonstrates stereotyped division timing (2, 3). Despite intensive studies on the regulation of cell fate differentiation, genetic control over temporal coordination of cell division during metazoan development is poorly understood. Timing of cell division is particularly critical during early developmental stages such as embryogenesis when cells undergo rapid division and migration, which is concomitant with cell fate differentiation.Because of technical challenges in quantifying cell division timing especially when an embryo undergoes rapid cell division, most of the studies on cell division timing focus on the earliest stage of development (4). For example, the first embryonic division in Caenorhabditis elegans produces two daughters, namely AB and P1, with differential developmental potential. The two cells also divide asynchronously with the ...
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