Unraveling the cellular and molecular dynamics of adult neurogenic niches and brain-body communication during regeneration

The regenerative potential of the adult brain lies within the neural stem cells (NSCs), a group of dormant cells capable of generating specialized neurons and glial cells.

NSCs are embedded in dedicated niches that are composed of heterogeneous cells, which provide a unique combination of signaling molecules and physical properties to support NSCs functions.

However, how niche cells remodel to promote complex NSC activation for repair and act as cohesive unit still remains elusive.

This project aims to delineate and genetically manipulate the niche cells in vivo and characterize their coordinated functioning in the transition of NSCs from quiescence to an active proliferative state during brain regeneration.

We will take advantage of recently identified quiescent NSC-like cells in the adult brain of genetically versatile fruit flies, which activate upon injury for regeneration and integrate similar features to their mammalian counterpart.While the niche provides local cues to articulate the proliferation in the NSCs, peripherical tissues are also affected upon brain damage.

Notably, metabolic relevant tissues as the adipose tissue and the gut are necessary to provide energy for the generation of new cells in the niches. However, which are the signaling molecules spanning upon damage and their source in the brain remains unknown. Thus, we propose to study the inter-organ crosstalk between the brain and other tissues during brain regeneration.

Overall, this work will provide detailed knowledge about cell interactions within the niches and inter-organ communication upon NSC activation in response to tissue damage.

By elucidating molecular and cellular mechanisms, this study aims to provide a comprehensive framework for harnessing the latent regenerative capacity of the brain, ultimately fostering advancements in regenerative medicine.