http://cercor.oxfordjournals.org/content/early/2012/08/14/cercor.bhs252.abstract
Abstract
The upper layers (II–IV) are the most
prominent distinguishing feature of mammalian neocortex compared with
avian or reptilian
dorsal cortex, and are vastly expanded in primates.
Although the time-dependent embryonic generation of upper-layer cells
is genetically instructed within their parental
progenitors, mechanisms governing cell-intrinsic fate transitions remain
obscure.
POU-homeodomain transcription factors Pou3f3 and
Pou3f2 (Brn1 and Brn2) are known to label postmitotic upper-layer cells,
and are redundantly required for their production.
We find that the onset of Pou3f3/2 expression actually occurs in
ventricular
zone (VZ) progenitors, and that Pou3f3/2
subsequently label neural progeny switching from deep-layer Ctip2+ identity to Satb2+
upper-layer fate as they migrate to proper superficial positions. By
using an Engrailed dominant-negative repressor, we show
that sustained neurogenesis after the deep- to
upper-layer transition requires the proneual action of Pou3fs in VZ
progenitors.
Conversely, single-gene overexpression of any Pou3f
in early neural progenitors is sufficient to specify the precocious
birth
of Satb2+ daughter neurons that extend
axons to the contralateral hemisphere, as well as exhibit robust
pia-directed migration that
is characteristic of upper-layer cells. Finally, we
demonstrate that Pou3fs influence multiple stages of neurogenesis by
suppressing
Notch effector Hes5, and promoting the expression
of proneural transcription factors Tbr2 and Tbr1.
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