How embryos establish a positional memory to enable adult regeneration.

Whitehead Institute For Biomedical Res, Cambridge MA

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Abstract

PROJECT SUMMARY/ABSTRACT The innovation of multicellular life presents with the unique challenge of establishing, organizing, and integrating information across various cell types. This is required to generate an initial pattern during development, maintain patterns during homeostasis, and reestablish patterns lost due to injury. These processes involve the production of specific differentiated cell types and proper three-dimensional tissue organization. How this is accomplished and faithfully recapitulated is a long-standing question in evolutionary and developmental biology. Whole-body regeneration is a feature present across metazoans and work in planarians has identified a population of pluripotent stem cells and key regulatory pathways important for patterning following injury. Although these signaling pathways are also seen in the context of embryogenesis, how adult tissues and stem cells re-access patterning information during regeneration is largely unknown. Importantly, these cells need to initiate a regulated proliferative and differentiation response, while mitigating the risk of proliferation from going awry. Recently it has been found that positional control genes (PCGs) required for planarian regeneration are expressed in muscle and upon injury dramatically alter their expression profiles. In this proposal, I will test the hypothesis that embryogenesis sets a positional memory in a particular lineage, establishing a mechanism to regenerate and properly pattern adult tissue. To this end, my specific goals are: (1) identify when and where positional information is established during development, (2) determine how muscle-specific PCGs instruct embryonic patterning, and (3) determine whether planarian embryogenesis co-opted adult regenerative patterning mechanisms. Overall, this proposal aims to provide a mechanistic understanding into how adult cells recall embryonic patterning instructions required for regeneration.