Feedback circuits are numerous in embryonic gene regulatory networks and offer a stabilizing influence on evolution of those networks.
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2023-06
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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 https://hdl.handle.net/10161/28310.
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Scholars@Duke
Gregory Allan Wray
I study the evolution of genes and genomes with the broad aim of understanding the origins of biological diversity. My approach focuses on changes in the expression of genes using both empirical and computational approaches and spans scales of biological organization from single nucleotides through gene networks to entire genomes. At the finer end of this spectrum of scale, I am focusing on understanding the functional consequences and fitness components of specific genetic variants within regulatory sequences of several genes associated with ecologically relevant traits. At the other end of the scale, I am developing molecular and analytical methods to detect changes in gene function throughout entire genomes, including statistical frameworks for detecting natural selection on regulatory elements and empirical approaches to identify functional variation in transcriptional regulation. At intermediate scales, I am investigating functional variation within a dense gene network in the context of wild populations and natural perturbations. My research leverages the advantages of several different model systems, but primarily focuses on sea urchins and primates (including humans).
David R. McClay
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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