Extracellular vesicles-mediated cross-talk during human brain development and disease

Introduction

Cellular cross-talk is an essential process influenced by numerous factors, including secreted vesicles that transfer nucleic acids, lipids, and proteins between cells. Extracellular vesicles (EVs) have been the center of many studies focusing on neuron-to-neuron communication. However, the role of EVs in progenitor-to-neuron and -astrocyte communication occurring during brain development has not been systematically investigated.

Importance of Extracellular Signals

Extracellular signals regulating the development of the brain are key players altered in many neurodevelopmental disorders (NDDs). Strikingly, we have found that more than 60% of the genes associated with NDDs encode for proteins that are loaded into EVs.

Research Objectives

With ExoDevo, inspired by new cell-non-autonomous mechanisms that we have identified as the cause of NDDs, I will investigate the role of EVs during brain development.

Focus Areas

I will focus on the physiological function of EVs that mediate the signals for cell-to-cell cross-talk and combine:

1. Transcriptomic analysis
2. Proteomic analysis
3. Imaging
4. Functional analysis of EVs derived from human cerebral organoids

This will open new avenues to tackle fundamental questions, such as how different cells communicate and provide feedback at different times and distances in the highly dynamic process of brain development.

Application to Neurodevelopmental Disorders

Ultimately, this will be investigated in human models of NDDs and will allow me to identify pathologically altered cellular cross-talk mediated by EVs. This knowledge of the cellular processes governing EV biology will provide the basis to better understand novel mechanisms underlying brain development and neurodevelopmental human pathologies.

Future Directions

Additionally, exploring new deliverable compounds for therapy will be a key aspect of this research. My expertise in human brain development and diseases, together with the possibility of combining multiple technologies, will be indispensable to achieve these essential goals.

Broader Impact

Meanwhile, exploring these novel aspects of brain development will bring me beyond my current research focus and broaden my perspectives on NDDs.