854A Poster - 13. Neural development and physiology
Thursday April 07, 2:00 PM - 4:00 PM

Unraveling the mechanisms of early neurogenesis with single cell resolution


Authors:
Ana Costa Veloso 1,2; Robert Zinzen 1,2

Affiliations:
1) Max Delbrueck Centre for Molecular Medicine (MDC), Berlin, Germany; 2) Berlin Institute for Medical Systems Biology (BIMSB), Berlin, Germany

Keywords:
o. stem cells; f. pattern formation

The Drosophila embryonic nervous system develops from neuroblast stem cells that emerge in a characteristic spatiotemporal pattern per segment. The lineage relationships from neuroblast to neurons and glia are highly stereotypic and have largely been described, but the underlying mechanisms driving diversification, specification and differentiation are still poorly understood.
To uncover how neuroblasts produce distinct lineage trajectories, we have produced a gene expression atlas resolving over 65 000 neurogenic stem cells across 6 consecutive timepoints encompassing all waves of neuroblast delamination. The resulting transcriptomic blueprint of neuroblasts and ganglion mother cells allows unique and novel insights into the molecular mechanisms responsible for early nervous system development.
We have been able to identify specific neurogenic populations and their gene expression dynamics along early neurogenesis. Our resource allows assigning spatial and temporal identities to individual cells and discovery of new spatio-temporal markers, including transcription factors and signaling molecules. Moreover, we show that the gene expression programs of individual neuroblast identities can be linked to specific upstream regulators and give new insights into the downstream effectors of cellular behavior. Several neuroblasts with glial potential were particularly interesting, as their glial character becomes manifest not only much earlier than expected, but temporal ordering indicates ‘developmental pockets’ of signaling receptivity. Finally, we demonstrate that newly identified drivers of neurogenesis are functionally important for crucial features of neurogenesis, such as proper motoneuron projection.
We present a resource that will aid in identifying neurogenic populations and individual neuroblasts, further our understanding of how individual neuroblasts diverge molecularly, allow discerning how their expression programs are regulated and how these differences drive the emergence of specific cell identities such as distinct motoneurons, interneurons, and glia.