Regulation of the protocadherin Celsr3 gene and its role in globus pallidus development and connectivity.

ABSTRACT: The globus pallidus (GP) is a central component of basal ganglia whose malfunctions cause a variety of neuropsychiatric disorders as well as cognitive impairments in neurodegenerative diseases such as Parkinson's disease. Here we report that the protocadherin gene Celsr3 is regulated by the insulator CCCTC-binding factor (CTCF) and the repressor neuron-restrictive silencer factor (NRSF, also known as REST) and is required for the development and connectivity of GP. Specifically, CTCF/cohesin and NRSF inhibit the expression of Celsr3 through specific binding to its promoter. In addition, we found that the Celsr3 promoter interacts with CTCF/cohesin-occupied neighboring promoters. In Celsr3 knockout mice, we found that the ventral GP is occupied by aberrant calbindin-positive cholinergic neu

SUBMITTER: Jia Z 

PROVIDER: S-EPMC4187713 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature