title: Molecular Determinants of Synaptic Specificity at the Single Cell Level
creator: Velten, Jessica
subject: ddc-570
subject: 570 Life sciences
description: The correct wiring of neuronal circuits represents one of the most complex processes throughout development. Mistakes in their formation underly genetic neuropathies including autism and schizophrenia, but the molecular program encoded in the genome allowing each axon to precisely innervate its target cell remains poorly understood.  In this thesis I use the Drosophila motoneuronal system as a tractable model for studying the formation of complex neuronal circuits during development. I profiled terminally specified motoneurons (MNs) of Drosophila embryos in multiple biological replicates by single cell RNA-Seqencing (scRNA-Seq), mapped their spatial position within the embryo through bioinformatic approaches and high-resolution imaging, and investigated cell-specific changes in synaptic wiring induced by genetic manipulations.  I demonstrate that the combinatorial expression of specific homeodomain transcription factors (TFs) serves as a molecular coordinate system to specify the identity and position of motoneuron identities along the ventral nerve cord (VNC). This TF factor code is linked to the expression of cell-specific combinations of Immunoglobulin (Ig) domain proteins that functionally determine synaptic specificity and synaptic partner choice by cell adhesion. My data also shows that a similar mechanism acts in muscle cells, suggesting that differential cell affinities encoded by Ig proteins downstream of homeodomain TFs is a key feature of selective synaptic partner choice. This suggests that a homeo-Ig code is translated into complex neuronal wiring schemes required for establishing the structure of neuronal circuits.  Together this thesis gives insights into the molecular logic of synaptic wiring down to the single cell level. In particular, the molecular determinates defining synaptic partners and instructing cells to form cell specific synaptic connections are identified. The experimental advances in this thesis enable a systematic view on spatial organization, molecular identities and connectivity of neuronal circuits during the development of an organism.
date: 2021
type: Dissertation
type: info:eu-repo/semantics/doctoralThesis
type: NonPeerReviewed
format: application/pdf
identifier: https://archiv.ub.uni-heidelberg.de/volltextserverhttps://archiv.ub.uni-heidelberg.de/volltextserver/29869/1/Dissertation_JessicaVelten.pdf
identifier: DOI:10.11588/heidok.00029869
identifier: urn:nbn:de:bsz:16-heidok-298695
identifier:   Velten, Jessica  (2021) Molecular Determinants of Synaptic Specificity at the Single Cell Level.  [Dissertation]     
relation: https://archiv.ub.uni-heidelberg.de/volltextserver/29869/
rights: info:eu-repo/semantics/openAccess
rights: http://archiv.ub.uni-heidelberg.de/volltextserver/help/license_urhg.html
language: eng