Summary
This project investigates how specific synaptic adhesion molecules (Ncam1, Cadm1, Cadm4) guide myelin formation on axons, using a zebrafish model to understand myelin abnormalities in neuropsychiatric disorders like autism spectrum disorder (ASD).
What they want
The project aims to determine whether Ncam1, Cadm1, and Cadm4 proteins guide myelin formation on specific axons. Researchers will use zebrafish to manipulate gene functions and observe axon-myelin interactions in living animals via confocal microscopy. Aim 1 involves using CRISPR-Cas9 mediated chromosomal insertion to create transgenic reporters for visualizing axon-myelin interactions and determining subcellular localization of adhesion proteins in oligodendrocytes. Aim 2 focuses on building a dual transgene system to create loss-of-function mutations of genes encoding Ncam1, Cadm1, and Cadm4 in oligodendrocyte lineage cells to assess their contribution to myelin abnormalities in ASD and other neuropsychiatric disorders.
Deliverables
- Transgenic reporters for visualizing gene expression and protein localization in vivo
- Loss-of-function mutations in oligodendrocytes for Ncam1, Cadm1, and Cadm4 genes
- Improved understanding of mechanisms regulating myelination
- Evidence regarding synaptic protein dysfunction's contribution to myelin abnormalities in disease
- New tools for future investigations of axoglial interactions
Technical requirements
- Zebrafish model system
- Confocal microscopy
- CRISPR-Cas9 mediated chromosomal insertion strategy
- Dual transgene system
