Abstract
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.
Highlights
Interneurons constitute a morphologically, neurochemically and functionally diverse group of cortical neurons that are essential modulators of neuronal activity in the cerebral cortex
To identify genes involved in migratory stream specification, we previously compared the gene expression profiles of cells in the pre-plate (PPL) zone with those of cells migrating through the intermediate zone (IZ) during early corticogenesis (E13.5)
We previously carried out a microarray analysis to identify genes that showed differential expression between the early tangential migratory streams, which may underlie the choice of pathway for migrating cortical interneurons (Antypa et al 2011)
Summary
Interneurons constitute a morphologically, neurochemically and functionally diverse group of cortical neurons that are essential modulators of neuronal activity in the cerebral cortex. Whilst many molecules have been identified as regulators of interneuron migration (Faux et al 2012; Marin 2013; Guo and Anton 2014), little is known about the factors that determine their choice of tangential migratory stream as they enter the cortex. Genetic differences between interneurons underlie their choice of one of the two early tangential pathways. To identify genes involved in migratory stream specification, we previously compared the gene expression profiles of cells in the pre-plate (PPL) zone with those of cells migrating through the IZ during early corticogenesis (E13.5). Our analysis identified several cadherin family members that showed differential expression, including Cdh, which was present only in the IZ at this stage (Antypa et al 2011), a finding recently supported by another study (Pensold and Zimmer 2018)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
