Feedback circuits are numerous in embryonic gene regulatory networks and offer a stabilizing influence on evolution of those networks.

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The developmental gene regulatory networks (dGRNs) of two sea urchin species, Lytechinus variegatus (Lv) and Strongylocentrotus purpuratus (Sp), have remained remarkably similar despite about 50 million years since a common ancestor. Hundreds of parallel experimental perturbations of transcription factors with similar outcomes support this conclusion. A recent scRNA-seq analysis suggested that the earliest expression of several genes within the dGRNs differs between Lv and Sp. Here, we present a careful reanalysis of the dGRNs in these two species, paying close attention to timing of first expression. We find that initial expression of genes critical for cell fate specification occurs during several compressed time periods in both species. Previously unrecognized feedback circuits are inferred from the temporally corrected dGRNs. Although many of these feedbacks differ in location within the respective GRNs, the overall number is similar between species. We identify several prominent differences in timing of first expression for key developmental regulatory genes; comparison with a third species indicates that these heterochronies likely originated in an unbiased manner with respect to embryonic cell lineage and evolutionary branch. Together, these results suggest that interactions can evolve even within highly conserved dGRNs and that feedback circuits may buffer the effects of heterochronies in the expression of key regulatory genes.





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Massri, Abdull Jesus, Brennan McDonald, Gregory A Wray and David R McClay (2023). Feedback circuits are numerous in embryonic gene regulatory networks and offer a stabilizing influence on evolution of those networks. EvoDevo, 14(1). p. 10. 10.1186/s13227-023-00214-y Retrieved from

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David R. McClay

Arthur S. Pearse Distinguished Professor of Biology

We ask how the embryo works. Prior to morphogenesis the embryo specifies each cell through transcriptional regulation and signaling. Our research builds gene regulatory networks to understand how that early specification works. We then ask how this specification programs cells for their morphogenetic movements at gastrulation, and how the cells deploy patterning information.
Current projects examine 1) novel signal transduction mechanisms that establish and maintain embryonic boundaries
mold the embryo at gastrulation; 2) specification of primary mesenchyme cells in such a way that they are prepared to execute an epithelial-mesenchymal transition, and then study mechanistically the regulation of that transition; 3) the specification of endoderm necessary for invagination of the archenteron; 4) formation of the oral/aboral ectoderm and the means by which patterning information is distributed three dimensionally around the embryo. That information is necessary for patterning and inducing skeletogenesis.
Other projects examine neural tube folding with the goal of identifying genes associated with neural tube defects. Finally, a large current effort in systems biology is being expended with the goal of enlarging our knowledge of early networks and how they interact.

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