In-TOX-icating neurogenesis

Abstract

Early development of the mammalian cerebral cortex proceeds via a sequence of proliferative and differentiative steps from neural stem cells toward neurons and glia. However, how these steps are molecularly orchestrated is still only partially understood. In this issue of The EMBO Journal, Artegiani and colleagues implicate Tox, a HMG-box transcription factor previously known only for its role in lymphocyte development, in early cortical development.

Figure 1

Off-switch type of Tox expression during cortical development The scheme illustrates the dynamically regulated expression of Tox in radial glia of the ventricular zone (referred to by the authors as proliferative progenitors or pp) and neurons in the developing cortical plate (CP) where Tox expression promotes neurite outgrowth. In Tbr2-positive progenitors (referred to by the authors as differentiative progenitors or dp) located in the subventricular zone (SVZ), Tox expression is absent. Likewise, young neurons migrating through the intermediate zone (IZ) do not express Tox. Forced expression of constitutively active Nfat4 (CA-Nfat4) induces Tox expression in the SVZ and inhibits neurogenesis. Intriguingly, direct Tox overexpression results in the emergence of cells suggestive (as indicated by the question mark) of basal radial glia characterized by Sox2 expression and the absence of Tbr2.