Cadherin 8 regulates proliferation of cortical interneuron progenitors

Cortical interneurons are born in the ventral forebrain and migrate tangentially in two streams at the levels of the intermediate zone (IZ) and the pre-plate/marginal zone to the developing cortex where they switch to radial migration before settling in their final positions in the cortical plate. In a previous attempt to identify the molecules that regulate stream specification, we performed transcriptomic analysis of GFP-labelled interneurons taken from the two migratory streams during corticogenesis. A number of cadherins were found to be expressed differentially, with Cadherin-8 (Cdh8) selectively present in the IZ stream. We verified this expression pattern at the mRNA and protein levels on tissue sections and found approximately half of the interneurons of the IZ expressed Cdh8. Furthermore, this cadherin was also detected in the germinal zones of the subpallium, suggesting that it might be involved not only in the migration of interneurons but also in their generation. Quantitative analysis of cortical interneurons in animals lacking the cadherin at E18.5 revealed a significant increase in their numbers. Subsequent functional in vitro experiments showed that blocking Cdh8 function led to increased cell proliferation, with the opposite results observed with over-expression, supporting its role in interneuron generation.