Cadherin-6 gene regulatory patterns in the postnatal mouse brain

Cadherin-6 (Cdh6, K-cadherin) is a synaptic adhesion molecule the expression of which demarcates restricted sets of neuronal circuitries in postnatal mouse brains. While roles for the cadherins in the formation and/or modulation of synaptic junctions have been implicated, that which drives cadherin expression along functional brain circuits has remained elusive. Here we investigate the genetic control of Cdh6 expression by applying a method that permits systematic integration of a reporter cassette into bacterial artificial chromosomes with extensive coverage of the huge Cdh6 gene locus, whereby the reporter activities are efficiently evaluated in stable transgenic mouse lines. Such screenings revealed that divisible genomic segments differentially control each brain region or nucleus specific expression of Cdh6 at the right phases for circuit formation. These separable regulatory modules for cadherin expressions tended to be grouped by working connectivities, suggesting their developmental and/or evolutional value in elaborating brain circuitry.