Regulation of astroglial branch morphogenesis during visual circuit assembly in Drosophila
Award Number
BB/S00386X/1Status / Stage
CompletedDates
1 December 2018 -30 November 2022
Duration (calculated)
03 years 11 monthsFunder(s)
BBSRC (UKRI)Funding Amount
£399,349.00Funder/Grant study page
BBSRC UKRIContracted Centre
The Francis Crick InstitutePrincipal Investigator
Dr Iris SaleckerWHO Catergories
Understanding Underlying DiseaseDisease Type
Dementia (Unspecified)CPEC Review Info
| Reference ID | 701 |
|---|---|
| Researcher | Reside Team |
| Published | 07/07/2023 |
Data
| Award Number | BB/S00386X/1 |
|---|---|
| Status / Stage | Completed |
| Start Date | 20181201 |
| End Date | 20221130 |
| Duration (calculated) | 03 years 11 months |
| Funder/Grant study page | BBSRC UKRI |
| Contracted Centre | The Francis Crick Institute |
| Funding Amount | £399,349.00 |
Abstract
Neural circuits are defined by the connectivity of diverse neuron subtypes and their close association with glia. Astrocytes form a heterogeneous glial population with remarkably complex and distinct shapes. Despite the importance of astrocytes for brain development and function, the mechanisms controlling the formation of their branches during development remain poorly understood. Using the Drosophila visual system as a genetic model, we have previously found that astrocyte-like medulla neuropil glia acquire stereotypic elongated morphologies with columnar and layered branching patterns in a stepwise fashion. Knockdown and loss-of-function analyses uncovered a novel role for the transmembrane Leucine-rich repeat protein Lapsyn in regulating branch morphogenesis and positioning of this astrocyte subtype. Using these findings as entry point, our proposal has the aim to answer the basic question how astrocytes acquire their distinct morphologies in interactions with neurons. To elucidate the molecular function of Lapsyn, we will first determine the differential requirement of protein domains to gain evidence for a role of this molecule as a receptor, co-receptor or structural cell surface molecule using genetic rescue approaches. Second, using mass spectrometry, we seek to identify candidates as potential in cis and in trans interacting molecules of Lapsyn in astrocytes and neurons, respectively. Third, using expression analyses, advanced genetic and biochemical approaches we will validate identified genes in detail. Utilizing binary expression systems, we will examine the impact of gene knockdown or loss in glia and neurons on glial branch morphogenesis. Finally, we will examine the role of correct astrocyte-like glia branch formation in regulating visual circuit connectivity and function, by examining links to synaptogenesis using electron microscopy techniques and responsiveness to neural activity using Calcium imaging.
Aims
our proposal has the aim to answer the basic question how astrocytes acquire their distinct morphologies in interactions with neurons.