Cortical neuron fate: early determination or progressive restriction?

The mammalian cortex is structured into defined layers of neurons and during development the excitatory neurons populating these layers arise in a stereotyped order – with deep layer neurons being born first, and upper layer neurons later. All these neurons derive from radial glial progenitors (RGPs), which produce intermediate progenitors (IPs) that in turn give rise to post-mitotic neurons. Two models have been proposed to explain fate determination in the cortex. In the ‘progressive fate restriction’ model, all RGPs are initially multipotent, but become fate restricted over time as they lose the ability to generate deep layer neurons. The ‘early fate restriction’ model, on the other hand, posits that RGPs are predetermined from an early stage to particular laminar fates. Anca Mihalas and Robert Hevner set out to test these contrasting models through clonal lineage tracing in the embryonic mouse cortex. Their careful analysis of IP-derived clones demonstrates that apoptosis of one daughter following IP division is a prevalent phenomenon, and suggests that upper layer fate-restricted RGPs are either absent or very rare in the early neocortex – thus supporting the progressive fate restriction model.