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Developmental logic of neurotransmitter specification

Developmental logic of neurotransmitter specification 

Supervisor: Dr Matthias Landgraf

 

Project summary:

A great deal is now known about neurogenesis, axon pathfinding and the emergence of neuronal networks. In insects, including Drosophila
melanogaster,
a conserved set of neuronal progenitors (neuroblasts) constitute the fundamental developmental units of the nervous system: each neuroblast produces a specific complement of nerve cells, each with particular projections. However, there remains a glaring gap in our understanding: how do
different cells adopt the synthesis of different neurotransmitters with which they communicate (e.g. excitatory, inhibitory, neuromodulatory)?

This lack of understanding has largely been due to a lack of suitable reagents with which to visualise faithfully transmitter choice. We recently developed genetic reagents for this very purpose, in collaboration with the White lab at the NIH.

We are now seeking to understand the developmental logic by which neuroblasts might produce neurons of just one or multiple transmitter types, the role of birth order or sibling cell competitive interactions in this process.

 

What the student will be doing:

This project takes advantage of state of the art genetic and imaging reagents developed by the Landgraf lab and their collaborators. The aim is to determine the patterning of transmitter specification across different neural lineages and within lineages. We plan to use live imaging to gain insight into birth order and sibling cell interactions leading to differences in transmitter expression.

 

References:

1. Diao, F. et al. Plug-and-Play Genetic Access to Drosophila Cell Types using Exchangeable Exon Cassettes. Cell Rep 10, 1410–1421 (2015).

2. Nern, A., Pfeiffer, B. D. & Rubin, G. M. Optimized tools for multicolor stochastic labeling reveal diverse stereotyped cell arrangements in the fly visual system. Proc Natl Acad Sci U S A (2015). doi:10.1073/pnas.1506763112

3. Schmid, A., Chiba, A. & Doe, C. Q. Clonal analysis of Drosophila embryonic neuroblasts: neural cell types, axon projections and muscle targets. Development 126, 4653–4689 (1999).

4. Baumgardt, M., Karlsson, D., Terriente, J., Díaz-Benjumea, F. J. & Thor, S. Neuronal subtype specification within a lineage by opposing temporal feed-forward loops. Cell 139, 969–982 (2009).