COMpetence of neural progenitors In Time

Objective

During brain development, neural progenitor cells generate an enormous diversity of neuronal subtypes in the correct numbers and proportions. Although the transition from progenitor cells to mature neurons is well studied, little is known about how plastic this process is among different progenitor populations and over time. COMIT aims to investigate the temporal dynamics of neural progenitor competence. Using the zebrafish embryonic brainstem the hindbrain as a model system and an innovative multicolour lineage tracing system TEMPO2.0, I will label and track different generations of specific neural progenitor populations as they progress through differentiation. Leveraging multiple transgenic zebrafish lines, I will monitor the contribution of these progenitors to glutamatergic and GABAergic neuron populations across different temporal windows. Further, I will challenge progenitor competence through heterochronical expression of temporal identity transcription factors, assessing their impact on neuronal subtype specification. Chromatin profiling will be employed to identify the genomic targets of re-specification factors, shedding light on the molecular mechanisms that regulate progenitor plasticity. This integrated approach, combining cutting-edge biocomputing, imaging, genetic, and molecular techniques, will provide key insights into the heterogeneity of neural progenitor competence and the mechanisms that control the generation of neuronal diversity. Ultimately, the findings from this research could pave the way for new cell therapy strategies targeting neurodevelopmental and neurodegenerative diseases.