Instrinsic an extrinsic influences on the lineage and mode of cell division of progenitors in the developing Zebrafish retina

• Antragstellerin: Professorin Lucia Poggi, Ph.D.
• Fachliche Zuordnung: Entwicklungsbiologie
• Förderung: Förderung von 2009 bis 2014
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 162243590

How do retinal precursors use intrinsic programming, extrinsic cues and asymmetric cell division to create distinct daughter cells with specific neural differentiation programs? Increasing evidence show that neural progenitors lineage follow pre-established intrinsic programs and suggest that intrinsic mechanisms, such as epigenetic modifications, might be at the heart of these programs. In addition, cell-cell interactions and extrinsic signals, such as the ones mediated by Notch signalling can modify neural fate decisions. The proposed research builds on our previous studies of the terminal divisions of retinal precursors expressing the basic helix-loop-helix (bHLH) transcription factor Ath5, which is essential for retinal ganglion cell (RGC) fate. We use the ex-utero, transparent zebrafish embryo, combined 4D video microscopy and genetic approaches to trace the fate of Eigenen Stelle Page 2 Lucia Poggi Ath5-precursors at their final mitosis. With this system, we began to elucidate the lineage and mode of cell division of retinal precursors, at the same time establishing a model system for the molecular genetic analysis of retinal progenitor lineage and plasticity in vivo. We are now ready to address specific questions such as: what is the sequence of cell-intrinsic events determining the lineage of Ath5-precursors in vivo? How are these events coupled to the asymmetric cell outputs of precursor cell divisions and are there cell fate determinants that become asymmetrically distributed between the daughter cells? How does Notch-Delta signalling affect the lineage of Ath5-precursors? Do epigenetic modifications take place in regulating the progression of Ath5-precursors through different competence states? This study will provide further insight into fundamental questions such as how multipotent stem cells can be encouraged to follow particular pathways of neuronal determination and differentiation.

• DFG-Verfahren: Sachbeihilfen