DS0405 -

Determination of the conserved CHOrdate genomic REgulatory LANDscape during embryogenesis – CHORELAND

Submission summary

During embryogenesis, a few number of signaling pathways conserved in all animals is constantly used and reused with slight differences in different lineages, to build the present morphological complexity of metazoans. The activation of these signals eventually leads to the expression of target genes in a cell and time specific manner. Gene expression is controlled by multiple cis-regulatory elements that are hierarchically packaged into chromatin in the so-called regulatory landscapes (RLs) If we want to understand the functional relationships existing between signaling pathways and the genes they regulate, we need to study how chromatin is structured and how this structure changes under different conditions.
We propose that: (i) chromatin packaging and occupancy by transcription factors plays a major role in gene expression regulation, (ii) changes in gene expression regulation during embryonic development in different animal lineages account for the morphological evolution in metazoans, (iii) thus, changes in chromatin packaging and accessibility during embryonic development of different animal lineages was instrumental for their morphological evolution, and (iv) the comparison between homologous loci in different animal lineages at homologous developmental stages should highlight conserved and divergent features that may give us some clues about how morphological evolution occurred.
The vertebrate body plan emerged from the basic chordate blueprint. The chordate phylum comprises three subphyla: the cephalochordates (amphioxus), the urochordates (tunicates), and the vertebrates. In addition to the chordate common morphological characteristics, a number of vertebrate-specific traits evolved during the Cambrian radiation and, today, one major question of evolutionary biologists is to understand how these vertebrate-specific traits appeared. Although tunicates are the sister group of vertebrates, they show very derived features, and cephalochordates were shown to be better suited to infer ancestral chordate traits from comparative analysis.
The goal of the present project is to establish the "conserved chordate genomic regulatory landscape" during embryogenesis. In other words, our objective is to decipher, at the genome level, changes in regulatory landscapes (RLs), linked to the activation/repression of the most important signaling pathways (i.e. retinoic acid, BMP, FGF, Nodal, etc) acting during embryonic development in two chordate animal models: the vertebrate zebrafish, and the cephalochordate amphioxus.
In order to understand the RLs modifications underlying embryonic development in both amphioxus and zebrafish to give new insights into the morphological evolution in the chordate lineage, we have divided the project in the following tasks:
Task1: Dynamic determination of chromatin landscapes in amphioxus and zebrafish during embryonic development. The aim is to determine the complete genomic regulatory landscape using ATAC-seq and transcriptomics for the main embryonic developmental stages in amphioxus and zebrafish.
Task2: Changes in chromatin landscapes under different experimental conditions. We will perform ATAC-seq and transcriptome analyses in embryos treated with molecules activating or inhibiting different major signaling pathways.
Task3: Establishment of the ancestral chromatin structure of chordates. Interspecies comparisons of RLs of orthologous genes will indicate the conservation/divergence of the regulation of these genes in chordates, and will allow us to establish ancestral versus derived regulatory logics of embryonic development in chordates.
Task4: Functional studies. The objective is to functionally test the regulatory landscapes obtained in WPs 1 and 2 in both amphioxus and zebrafish.
This comparative study between two chordates that diverged more than 500Mya will highlight conserved versus lineage-specific changes that might explain the appearance of morphological innovations in vertebrates.

Project coordination

Hector ESCRIVA (Biologie Integrative des Organismes Marins)

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.

Partner

CABD, CSIC Centro Andaluz de Biologia del Desarrollo
BIOM, UMR7232 CNRS/UPMC Biologie Integrative des Organismes Marins

Help of the ANR 268,712 euros
Beginning and duration of the scientific project: December 2016 - 36 Months

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