Abstract
Pyramidal neurons in the deep layers of the cerebral cortex can be classified into two major classes: callosal projection neurons and long-range subcortical neurons. We and others have shown that a gene expressed specifically by subcortical projection neurons,
Fezf2
, is required for the formation of axonal projections to the spinal cord, tectum, and pons. Here, we report that
Fezf2
regulates a decision between subcortical vs. callosal projection neuron fates.
Fezf2
−/−
neurons adopt the fate of callosal projection neurons as assessed by their axonal projections, electrophysiological properties, and acquisition of Satb2 expression.
Ctip2
is a major downstream effector of
Fezf2
in regulating the extension of axons toward subcortical targets and can rescue the axonal phenotype of
Fezf2
mutants. When ectopically expressed, either
Fezf2
or
Ctip2
can alter the axonal targeting of corticocortical projection neurons and cause them to project to subcortical targets, although
Fezf2
can promote a subcortical projection neuron fate in the absence of Ctip2 expression.