Figure 7.

Model of DG morphogenesis and Cux2 activity in perinatal hippocampus progenitors. A: Schematic of DG morphogenesis in the rodent brain. The first wave of granule cell precursors arises at fetal stages (E15.5 in the mouse) and migrates away from the 3rd ventricle (3rdV) region to populate the growing subventicular (SVZ) dentate matrix in the medial region of the telencephalon. These cells are fated to give rise to the outer-most granule cell neurons. As DG development continues within the first few weeks of life, a second germinative matrix forms deep within in the SVZ of the medial telencephalon. This is the dentate knot. Cux2 activity is high at these early stages of DG morphogenesis. As the animal progresses to adulthood, the tertiary germinative matrix forms and becomes populated with long-lived multipotent NPs. This region is the SGZ that houses Type 1 cells capable of giving rise to nascent neurons well into adult life. B: Model of Cux2 localization is a subset of Type 1 progenitors that originate in the dentate germinal regions at fetal stages and persists to the first weeks of life. This is a transitory progenitor that is transiting from a Type 1-like Nestin+/GFAP+/Sox2+ radial glia to a Sox2+ Type 2 cell, which lack a radial process and astroglial markers. Cux2 was also detected in DCX⁺ neuroblasts (Type 3 cells) and immature newly formed granule cells identified by Calretinin expression. Fate mapping of Cux2-expressing progenitors revealed labeling of Calbindin-positive DG cells, and not SGZ progenitors, suggesting that the Cux2⁺ progenitor does not self-renew and directly generates granule cells. Abbreviations as in Figure 3. [Color figure can be viewed in the online issue, which is available at http://wileyonlinelibrary.com.]