YAP Activity Is Necessary and Sufficient for Basal Progenitor Abundance and Proliferation in the Developing Neocortex

摘要

Neocortex expansion during mammalian evolutionhas been linked to an increase in proliferation ofbasal progenitors in the subventricular zone. Here,we explored a potential role of YAP, the major downstreameffector of the Hippo pathway, in proliferationof basal progenitors. YAP expression and activity arehigh in ferret and human basal progenitors, whichexhibit high proliferative capacity, but low in mousebasal progenitors, which lack such capacity. Conditionalexpression of a constitutively active YAP inmouse basal progenitors resulted in increased proliferationof basal progenitor and promoted productionof upper-layer neurons. Pharmacological and geneticinterference with YAP function in ferret andhuman developing neocortex resulted in decreasedabundance of cycling basal progenitors. Together,our data indicate that YAP is necessary and sufficientto promote the proliferation of basal progenitors andsuggest that increases in YAP levels and presumablyactivity contributed to the evolutionary expansion ofthe neocortex.