Gene Regulatory Networks during Development

on 7th of November, 2007 in Of Interest
About the Author:
Dan is a postdoc working at the University of Cyprus in developmental biology. He has a BSc in molecular biology and a PhD pharmacology and biochemistry.

Gene regulatory network (GRN) circuits are collections of DNA segments in a cell which interact with each other (indirectly through their RNA and protein expression products) and with other substances in the cell, thereby governing the rates at which genes in the network are transcribed into mRNA. A lot of research has gone into (a) identifying components of GRNs and (b) developing mathematical models describing their dynamic spatial and temporal interactions. Molecular and cell biologists have a lot to offer in explaining embryonic development from the former perspective.

Eric Davidson's lab at Caltech has been working on this for a few years, with a recent paper in Science on such findings in sea urchin embryos.

Specification of future tissues of the early sea urchin embryos is embodied in one such GRN, which describes the interactions of about 50 genes encoding transcription factors. Joel Smith et al. of Davidson's lab focused on one GRN subcircuit, the function of which is to direct a dynamically expanding ring or torus of regulatory gene transcription early in embryogenesis. The result is specification of distinct lineages in separate endomesodermal territories (Figure 1 from the paper, below). Within the uncovered GRN subcircuit, three genes were found to be primarily implicated: wnt8, blimp1 and otx.

grn

Smith et al. summarize:

The genomic regulatory code is a static linear structure, whereas embryonic development is intrinsically a process driven by dynamically changing regulatory states. Here, we resolved a gene regulatory network subcircuit that combines these aspects in one small apparatus. The subcircuit's kinetics depend on the synthesis and turnover rates of the relevant mRNAs and proteins, as well as on the affinities of the transcription factors for their cis-regulatory target sites. What the apparatus does, however, depends on the genomic cis-regulatory sequence of the blimp1 and wnt8 genes, where its unique features, its feedback loops, AND gates, and autorepression function are encoded.

Commentary

Complex and sounding like something out of electrical engineering. Pretty frightening stuff to most people – no wonder why laypeople na??vely find this sort of thing as evidence for intelligent design. Despite the language borrowed from engineering however, GRNs such as these are chemical in nature and not mechanical.

This particular GRN subcircuit doesn't look all that different from the basic Lac operon. Oh, some control mechanisms have been acquired over time, to tweak the coordination of many cells at once. The fundamentals of feedback loops, AND gates, and autorepression are still all there however.

  • Smith J, Theodoris C, Davidson EH. A Gene Regulatory Network Subcircuit Drives a Dynamic Pattern of Gene Expression. Science, 2 Nov 2007. 318(5851): 794-797. doi: 10.1126/science.1146524
  • Davidson EH. The Regulatory Genome: Gene Regulatory Networks in Development and Evolution. (Academic Press, San Diego, CA, 2006)

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