Benutzerspezifische Werkzeuge

A25: Towards a morphological and evolutionary understanding of non-apical progenitors in the zebrafish retina

Project leader: Dr. C. Norden 

The retina as an outpocketing of the central nervous system (CNS) has proven to be an excellent model for studying brain development due to its easy accessibility and the fact that it features the complexity of five different kinds of neurons within a rather confined space. Understanding general developmental programs in the retina generates important insights in understanding other, less accessible parts of the CNS. For example the ratio of apically versus basally dividing progenitors, one aspect extensively studied to understand the evolutionary expansion of the CNS, has so far mainly been studied in the neocortex that is hard to access.

These questions are important however as it is assumed that especially basally dividing progenitors play a role in brain expansion over evolution. So far, little attention has been paid to understand the emergence and necessity of basal progenitors in retinal development. Until recently it was assumed that all retinal neurons derive from apical division of multipotent progenitors. A couple of years ago however, Godinho et al. showed that non-apically dividing progenitors give rise to the horizontal cell (HC) layer. Our lab has extended on this finding. We found that more cell types than previously assumed can be generated by basal divisions of retinal precursor cells. This analysis sheds new light onto the general birth order of retinal neurons and expands on the findings based on apically dividing cells.

We now want to elaborate on our initial results and analyse basal progenitor appearance in relation to cellular as well as tissue constraints. Furthermore, as cell cycle phase length variations have been implicated in proliferation versus differentiation decisions of precursor cells, we also aim to compare the cell cycle kinetics of the basally dividing progenitor cells to cell cycle kinetics of apical progenitors. We also want to characterize whether retinal sub-apical divisions occur during regeneration scenarios and whether they are conserved over evolution or are a zebrafish specific phenomenon. Answering these questions is crucial to understand the emergence of basal progenitors during retinal development, their necessity and contribution to retinal development and might give insights on whether such progenitors are a broader phenomenon in multiple locations of  brain development than previously assumed.

 

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Funding program:

DFG