Neural circuits revealed by axon tracing and mapping cadherin expression in the embryonic chicken cerebellum

Abstract

Fiber connections of the cerebellar cortex are organized into distinct parasagittal domains. Each domain expresses a unique subset of various genes. Brain structures that are directly connected to the cerebellar cortex, such as the deep cerebellar nuclei and the inferior olivary nucleus, show a similarly differential pattern of connectivity and gene expression. For example, several members of the cadherin family of adhesion molecules are expressed differentially in the subdivisions of the cerebellar system in chicken and mouse. Little is known, however, about how the molecular maps in the different parts of the cerebellum relate to each other in terms of connectivity. Here, we mapped the expression of three cadherins (cadherin-8, protocadherin-7, and protocadherin-10) in the cerebellar system of the chicken embryo. By simultaneously tracing axonal connections with biotinylated dextran amine, we demonstrate that cortical domains and deep nuclear portions as well as their fiber connections have a matching expression profile for protocadherin-10 in the posterior part of the cerebellum. Based on the tracing results for protocadherin-10 and the comparative expression mapping of all three cadherins, the cortical projection domains of the three deep cerebellar nuclei were determined in the posterior part of the cerebellum. Results were extrapolated to the rest of the cerebellar cortex. Our results provide direct experimental support for the notion that cadherins are markers for neural circuits in the brain. Moreover, we show that the expression pattern of all three cadherins confers unique identities to the Purkinje cell domains.