Project Summary/Abstract
Organisms with regenerative abilities have been informative models for uncovering natural
mechanisms by which tissue damage activates stem or progenitor cells for injury repair. Such
systems require not only sources for newly forming differentiated cells and initial responses to
wounding, but also critically, spatial information systems that signal tissue presence/absence in
order to control appropriate regeneration outcomes and restore tissue to its original scale and cell
number. While regenerative tissues have been extensively probed for the roles of injury-induced
signals and the involvement of stem or progenitor cells, much less is known about the molecular
and developmental processes that enable the restoration of form after injury and its maintenance
through adult growth. This grant seeks to understand the factors involved in the early symmetry-
breaking events after injury, the process of establishing and using signaling centers for control of
regenerative growth, the mechanism by which whole-body regeneration can robustly restore
tissue proportionality and restore homeostasis, and identify the control mechanisms used by
progenitor cells in whole body regeneration. The work will compare regeneration mechanisms in
two distantly evolved model systems, the planarian Schmidtea mediterranea and the acoel
Hofstenia miamia, each capable of whole-body regeneration using Piwi-expressing pluripotent
adult stem cells termed neoblasts. Using expression profiling, RNAi screening and spatial
transcriptomics, these studies will reveal what factors and strategies of whole-body regeneration
are ancient and conserved. These approaches will reveal foundational mechanisms used by
organisms to control adult tissue repair, growth, and homeostasis.