, 1993 and Takahashi et al., 1994). Subsequent work has shown that G1 lengthening acts to promote neurogenesis during development of the mammalian cerebral cortex (Lange et al., 2009) and is not simply a passive consequence of the switch to neurogenesis. More recently, it has been found that the increase in G1 is due to an increase in the genesis of basal progenitor cells that have a relatively long G1 phase from apical progenitor cells that have a shorter G1 phase (Arai et al., 2011). In addition, an extended S phase is found in cortical stem cells that expand the stem cell pool as opposed to click here those destined to generate

neurons. The latter observation has been suggested to reflect the greater need for careful quality control of DNA replication in expanding stem cells than in stem cells about to undergo a terminal division to generate two postmitotic neurons (Arai et al., 2011). Optic lobe neuroepithelial cells also undergo a transient cell-cycle arrest prior to adopting the neuroblast fate (Hofbauer and Campos-Ortega, 1990, Orihara-Ono et al., 2011 and Reddy et al., 2010). G1 arrest is induced through downregulation of the Fat-Hippo signaling pathway (Orihara-Ono et al., 2011 and Reddy et al., 2010). Expression of a constitutively

activated form of Yorkie (Yrk), a transcription factor controlled by Fat-Hippo signaling, prevents the cell-cycle arrest and blocks the transition from neuroepithelial cell to neuroblast. Similarly, in the chicken neural tube overexpression of Yes-associated this website protein (YAP, the vertebrate ortholog of Yrk) results in the expansion of the neural progenitor pool at the expense of differentiating cells (Cao et al., 2008). Recent results suggest that FatJ, the closest vertebrate homolog to Drosophila Fat, regulates Yap in the vertebrate neural tube ( Van Hateren et al., 2011).

In the Drosophila optic lobe as well as in the chicken neural tube YAP/Yrk positively regulates cell-cycle regulators to accelerate cell-cycle progression during early to mid-G1. Overall, it others is clear that the complex interplay between cell-cycle regulation and cell-fate determination systems is a common feature of neural stem cells in vertebrates and invertebrates. During asymmetric cell division in some cell types, the nonrandom segregation of mother versus daughter centrosomes has been observed to correlate with differences in cell fate (reviewed by Macara and Mili, 2008). The functional importance of centrosomes in neural stem cell self-renewal is evident from primary microcephaly (MCPH), an autosomal-recessive human condition in which the entire brain, and to a greater degree the cerebral cortex, are reduced in size (Thornton and Woods, 2009). Of the eight known MPCH loci, disease-causing mutations have been found in six genes, all of which encode proteins found in centrosomes (such as ASPM; Bond et al.