Tom Maniatis - The Protocadherin Gene Cluster: A Bar Code Generator for Single Neuron Self-Recogniti

Professor Maniatis discussed the mechanisms by which clustered Pcdh genes regulate the distribution of serotonergic neurons in the brain. He emphasized the importance of individual neurons accurately distinguishing "self" from "non-self", and mechanisms that prevent neurites from the same neuron to form synaptic connections. Through their research, Professor Maniatis's team discovered that the protocadherin (Pcdh) gene cluster, divided into Pcdh-α, Pcdh-β, and Pcdh-γ regions, provide a "bar code" for single neuron self-recognition. Subsequent studies revealed the function of Pcdhs in the wiring of olfactory sensory neurons (OSN) and serotonergic neurons, highlighting the role of Pcdhs' diversity in the assembly of cell surface molecules. In cases of diversity loss, OSNs failed to correctly connect in the brain, leading to an inability for mice to distinguish different odors. Through extensive research, Professor Maniatis's team identified a single gene within the Pcdh cluster, Pcdh-α-ac2, responsible for the ability of serotonergic neurons to assemble in a tiled pattern throughout the brain, ensuring the even distribution of serotonin. Deleting Pcdh-α-ac2 caused serotonergic neurons to become entangled, resulting in depressive symptoms in mice. These studies provided new insights into the study of brain diseases, suggesting that abnormalities in neuronal wiring may be related to various neurological disorders.