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Understanding the evolution of regeneration-permissive gene expression and positional memory in Axolotl limb regeneration

Ziel

Molecular studies of development in diverse animal models have revealed the remarkably conserved set of morphogens governing growth and patterning of body axes and organ fields. Equally astounding is the diversity of form and function arising from the implementation of these morphogens. The systematic analysis of well-defined traits in closely related species has revealed how changes in gene regulatory sequences and their trans-acting factors have yielded diversity. An important future challenge is to understand, at the genome level, the evolution of animal form in situations where such a rich set of closely related species may not be available.

Vertebrate limb regeneration is a particularly fascinating yet challenging context to pursue the evolution of traits related to controlling the body plan. Amputation of the Axolotl limb results in the formation of a limb blastema that morphologically and molecularly resembles the embryonic limb bud. In this system, the limb morphogen network must be reactivated only upon tissue removal and not wounding, but also corresponding to a positional memory existing in the adult tissue. These signalling cassettes must also be deployed in a way that can scale to the size of a blastema that is vast when compared to an embryonic limb bud. An important question is whether and how the limb development network has diverged to accomodate these unique traits.

During Axolotl limb development and regeneration, some key limb morphogens display divergent expression patterns compared to other vertebrates. I hypothesize that this divergent expression has functional importance for allowing limb regeneration. My goal is to 1) understand how this divergent expression arose 2) functionally test its role in regeneration specificity and scaling, and 3) use the system to dissect the molecular nature of positional memory that is critical for regeneration. I refer to this work as “evo-reg”.

Finanzierungsplan

ERC-ADG - Advanced Grant

Gastgebende Einrichtung

FORSCHUNGSINSTITUT FUR MOLEKULARE PATHOLOGIE GESELLSCHAFT MBH
Netto-EU-Beitrag
€ 2 325 659,00
Adresse
CAMPUS-VIENNA-BIOCENTER 1
1030 Wien
Österreich

Auf der Karte ansehen

Region
Ostösterreich Wien Wien
Aktivitätstyp
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Links
Gesamtkosten
€ 2 325 659,00

Begünstigte (1)