369B Poster - 04. Stem cells, regeneration and tissue injury
Friday April 08, 2:00 PM - 4:00 PM

Authors:
Fiona Kerlin; Robert Zinzen

Affiliation: Max Delbrück Center for Molecular Medicine in the Helmholtz Association Berlin-Mitte (BIMSB)

Keywords:
c. neural stem cells; d. neuronal specification

During embryogenesis in Drosophila melanogaster, a tightly controlled gene regulatory network generates a specific number of neurogenic stem cells, also called neuroblasts, in distinct positions over the course of early development. This process of neurogenesis generates a total of ~30 neuroblasts per segment in a spatially and temporally controlled manner, where neuroblasts are successively selected and delaminate from an epithelial sheet of cells along 3 dorsoventral columns and several anteroposterior rows. Once born, neuroblasts divide asymmetrically several times to self-renew and produce ganglion mother cells, neurons, and glia. This series of events is characterized by a temporally and spatially distinct gene expression, so that each neuroblast has a unique pattern of gene expression that determines its developmental trajectory. Importantly, the spatial and temporal origin of the neuroblast is thought to determine its ensuing lineage and cell fate.
After decades of research the neurogenic system in the early Drosophila embryo is quite well understood phenomenologically: Not only are we aware of many gene expression combinations that are distinct for individual neuroblasts, but fluorescent labeling experiments of individual neuroblasts have yielded maps of their developmental trajectories. However, our understanding of the molecular mechanisms that restrict, drive and distinguish neuroblast fate decisions is extremely limited.
New studies in my lab using single-cell sequencing are for the first time able to assess the genome-wide gene expression complements of individual neuroblast identities with the aim to determine the expression of factors that delineate these identities.
Mapping cell fate decisions over the course of embryonic neurogenesis of Drosophila will allow for a more comprehensive understanding of lineage decisions that give rise to the emerging neurogenic cell identities in the early nervous system. My aim is to reveal the exact lineages that give rise to neurons and glia with spatial resolution in vivo.
Specifically, the building of a lineage tree for neuroblasts will allow to infer a relatedness of the cells to each other. So far only the common ancestry of cells could be shown, but not when and in which succession those cells separated from each other.
I aim to map lineage decisions and couple the description of lineages with knowledge of when and where molecular markers are expressed.
The lineage of neuroblasts will be recorded with the intMEMOIR method, that relies on a genomic editing process via an integrase and makes cells express the resulting barcode. Image acquisition of the barcode transcript with RNA in situ hybridization will be followed by lineage tree modelling. This should lead to the identification of new marker genes and foster a more detailed understanding about the underlying molecular mechanisms that drive early neurogenic trajectories.