DSCAM
Description
The DSCAM (DS cell adhesion molecule) is a protein-coding gene located on chromosome 21.
DSCAM is a gene that encodes one of several protein isoforms. It plays a crucial role in the development of Down syndrome (DS), the most common birth defect associated with intellectual disability. DSCAM is expressed in the developing nervous system, with the highest level of expression occurring in the fetal brain. When over-expressed in the developing fetal central nervous system, it leads to Down syndrome. DSCAM is a homologue of the Dscam protein in Drosophila melanogaster, which has 38,016 isoforms arising from alternative splicing. This diversity allows every neuron in the fly to display a unique set of Dscam proteins on its cell surface, contributing to neuronal self-avoidance mechanisms essential for normal neural circuit development. The DSCAM protein structure is conserved across diverse species, suggesting an ancestral origin dating back over 600 million years.
DSCAM is a cell adhesion molecule that plays a crucial role in neuronal self-avoidance. It promotes repulsion between specific neuronal processes of either the same cell or the same subtype of cells, ensuring proper neural circuit development. In the retina, DSCAM mediates both isoneuronal and heteroneuronal self-avoidance, leading to an orderly dendritic arborization and mosaic spacing between amacrine and ganglion cell bodies. It acts as a receptor for netrin, essential for axon guidance, both independently and in collaboration with the DCC receptor. DSCAM may also cooperate with UNC5C in NTN1-mediated axon repulsion independently of DCC. During spinal cord development, DSCAM guides commissural axon projection across the ventral midline to reach the floor plate upon ligand binding. It also activates intracellular signaling pathways involving MAPK8 and p38 MAP kinase. DSCAM promotes lamina-specific synaptic connections in the retina, being expressed in specific subsets of interneurons and retinal ganglion cells (RGCs) and promoting synaptic connectivity via homophilic interactions.
DSCAM is also known as CHD2, CHD2-42, CHD2-52.
