A new way of looking at neurogenesis at the apical surface

Abstract

The development of the mammalian brain requires a large expansion of the neural cell‐progenitor pool followed by terminal differentiation. One of the most general and fundamental mechanisms that regulates the conversion of undifferentiated neural stem cells and progenitor cells to differentiated neurons and glia is the conversion of the orientation of mitotic cleavage, which leads to a change from symmetric to asymmetric cell division. Proliferating neural stem cells divide symmetrically during early mammalian neurogenesis to increase the progenitor pool, whereas both symmetric (proliferative) and asymmetric (neurogenic) mitosis occur later in neurogenesis to generate neural stem cells and post‐mitotic neurons or glia, respectively (Noctor et al , 2004; Gotz & Huttner, 2005). During cell division at the apical (ventricular) surface of the brain, the proliferating neuroepithelial cells and the radial glial progenitors have a distinct apico‐basal polarity and an elongated radial morphology (Kosodo et al , 2004; Gotz & Huttner, 2005). The disruption of mitotic spindle orientation during neurogenesis results in proliferation and cell‐fate defects, supporting the importance of controlling symmetric and asymmetric division to determine cell fate. For example, loss of the G‐protein‐regulator complex LGN (Leu–Gly–Asn repeat‐enriched protein)/AGS3 (activator of G‐protein signalling 3)—also known as Gpsm2 (G‐protein‐signalling modulator 2)/Gpsm3—or the loss or reduction of LIS1 (Lissencephaly 1), which is a noncatalytic subunit of the platelet‐activating factor acetylhydrolase Ib, results in randomized spindle orientation during apico‐basal division and causes changes in the cell‐fate decisions of radial glial progenitors (Konno et al , 2008; Yingling et al , 2008). Although the importance of symmetric and asymmetric …