How does gene circuitry specify and pattern embryonic development?
What is the nature of the events set in motion by the expression of a single developmental “master regulator”? Is there a common set of optimal regulatory interactions (rules), analogous to evolutionarily conserved master regulatory genes, which operate among the targets of master regulators to enable developmental robustness and evolvability?
To address these questions we are studying the activity of pal-1 , the C. elegans Caudal homolog, an ancient homodomain protein that specifies and patterns posterior development in animals. In C. elegans pal-1 is necessary and sufficient to specify the identity of the C blastomere, a posterior cell in the 8-cell embryo, and then to control its subsequent development or cell lineage. Our goals are to generate a systems-level description of the gene circuitry (network topology) initiated by pal-1 activity and then to infer and test functional units (modules) that enable pal-1 to robustly specify posterior development. We have used microarrays, reporter genes, and RNAi to both identify the initial targets of pal-1 activity in the early embryo and to assemble these genes onto a regulatory framework. Many of these genes are expressed in descendants of other blastomeres and the primary cell types, muscle and skin, descended from the C blastomere are not unique to the C lineage. Thus, we are currently employing computational and a myriad of experimental approaches to understand how muscle- and skin-specific networks are established and maintained (insulated from each other). A global question is whether there are predictable (evolutionarily conserved or optimal natural solutions) regulatory interactions or whether every cell/lineage/organism employs a unique solution. Towards this goal we are comparing the topology of the C-lineage regulatory network between morphologically indistinguishable nematodes species whose genomes have been evolving independently for ~100,000,000 years.
Participating Lab Members:
|Diana Caracino||Regulation of translation in the early embryo|
|Katerina Ragkousi||Examining whether the activity of a wingless homologue is required for cell fate specification within the C lineage|
|Casey Roehrig||Examination of genes involved in muscle specification|
|Shai S. Shen-Orr||Computational approaches to understanding transcript regulation in the embryo|
|Jessica Smith||Studying interactions between transcription factors in the C-lineage regulatory network|
|Itai Yanai||An evolutionary approach to understanding the C. elegans transcriptome.|