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Does regeneration re-use developmental gene regulatory networks?
Funder: French National Research Agency (ANR)Project code: ANR-23-CE13-0028
Funder Contribution: 479,238 EUR
Description

Some animals have the capacity to regenerate their organs with a high degree of fidelity during adult life; the regenerated organs are precise replicas of those originally produced during embryonic development. Does this capacity result from the re-use of embryonic gene regulatory networks (GRNs), or have these animals evolved GRNs that are unique to regeneration to produce the same structure? Our project will address this question in the crustacean Parhyale hawaiensis, an emerging experimental model for studying leg regeneration. Parhyale can regenerate their legs with high fidelity, throughout their lifetime. First, we will collect data on the chromatin accessibility and gene expression profiles from tens of thousands of cells at different time points during the course of leg development and regeneration. In parallel, we will determine the DNA binding preferences of the entire repertoire of transcription factors expressed at relevant stages. These data will serve as the basis for inferring the GRNs that underpin leg development and regeneration, by correlating the expression of transcription factors with patterns of chromatin accessibility and expression of putative target genes, using established methods. We will compare the predicted GRNs of development and regeneration to identify shared and divergent elements. We will validate key nodes of these GRNs experimentally using transgenic approaches. Discovering whether regeneration recapitulates development is a key for understanding the genetic underpinnings and the evolutionary dynamics of regeneration.

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