The Generation of Superficial Cortical Layers Is Regulated by Levels of the Transcription Factor Pax6

Abstract

The ventricular zone (VZ) of the embryonic dorsal telencephalon is a major site for generating cortical projection neurons. The transcription factor Pax6 is highly expressed in apical progenitors (APs) residing in the VZ from the earliest stages of corticogenesis. Previous studies mainly focused on Pax6(-/-) mice have implicated Pax6 in regulating cortical progenitor proliferation, neurogenesis, and formation of superficial cortical layers. We analyzed the developing cortex of PAX77 transgenic mice that overexpress Pax6 in its normal domains of expression. We show that Pax6 overexpression increases cell cycle length of APs and drives the system toward neurogenesis. These effects are specific to late stages of corticogenesis, when superficial layer neurons are normally generated, in cortical regions that express Pax6 at the highest levels. The number of superficial layer neurons is reduced in postnatal PAX77 mice, whereas radial migration and lamina specification of cortical neurons are not affected by Pax6 overexpression. Conditional deletion of Pax6 in cortical progenitors at midstages of corticogenesis, by using a tamoxifen-inducible Emx1-CreER line, affected both numbers and specification of late-born neurons in superficial layers of the mutant cortex. Our analyses suggest that correct levels of Pax6 are essential for normal production of superficial layers of the cortex.

Drosophila Pax6 promotes development of the entire eye-antennal disc, thereby ensuring proper adult head formation

“…This observation directly supports our model that Ey/Toy control growth of the eye-antennal disc and is consistent with studies in vertebrates that demonstrate roles for Pax6 in the proliferation of neural progenitors within the brain (53,(78)(79)(80). Earlier studies observed cells undergoing apoptosis in Pax6 singlemutant eye-antennal discs and showed that blocking cell death alone can partially rescue the head defects of the ey D and toy hdl mutants (46).…”

Taurine Inhibits K+-Cl− Cotransporter KCC2 to Regulate Embryonic Cl− Homeostasis via With-no-lysine (WNK) Protein Kinase Signaling Pathway

“…6A). These GFP signals colocalized with Cux1, which is known to be expressed in several cortical surface layers (II/III and IV after laminar organization) (71,72), but not with Tbr1, a marker of deep cortical layers (Fig. 6, B and C) (72,73 …”

Gde2 regulates cortical neuronal identity by controlling the timing of cortical progenitor differentiation

“…Our efforts to determine whether the length of the cell cycle is altered in the absence of Gde2 using a well-established paradigm involving spaced consecutive injections of IdU and BrdU showed no differences in cell-cycle length between Gde2 -/-and WT animals (M.R., J.C., S.P. and S.S., unpublished observations) (Georgala et al, 2011). A caveat of this approach is that it assumes that all progenitors share uniform cell-cycle parameters, which might not be the case in Gde2 -/-cortices given the changes in cellcycle exit in these animals that are superimposed on normal variations of cell-cycle length over time.…”