This difference of 5–10 days is probably critical because heterotopic grafts of rat E12 cortex target subcortical regions defined by the recipient graft site, whereas the targets of rat E14 grafts are defined by the cortical area from which the donor cells originated (Gaillard et al., 2003 and Pinaudeau et al., 2000). Whether the respecification occurred at the level of progenitor cells or the neurons produced by them was not determined, but it seems likely that rat E12 neural progenitor cells are still capable of responding to the morphogen DAPT in vivo gradients present within in the developing cortex by adjusting their transcription factor

levels, whereas the areal identity of rat E14 progenitor cells is fixed. E12 and E14 in the rat are equivalent to ∼E10.5 and ∼E12.5 in the mouse (Schneider and Norton, 1979), and mouse subcortical projection neurons are not produced until after E12.5 (Polleux et al., 1997 and Takahashi et al., 1999). Thus, the areal identity of mouse cortical progenitor cells is probably fixed by E12.5, and the transplanted cells of Ideguchi et al. (2010) presumably selleck compound had not yet reached this stage. More detailed analyses will be needed to

precisely determine the stage of neural differentiation at which targeting potential becomes fixed and to learn the molecular changes responsible for this loss of plasticity. The plasticity of early cortical neuroepithelial cells may present an opportunity to circumvent the requirement for areal specification in vitro if cells are transplanted after dorsal telencephalic fate is fixed, but while areal identity is still plastic. However, this strategy would entail losing the ability to transplant a single neuronal subtype given that early cortical progenitors will likely proceed through the known temporal sequence of neuronal subtype production—a drawback in some situations. There may also be less control over the final dose of transplanted cells because ADAMTS5 proliferation will occur after transplantation. Finally, the less

differentiated and more proliferative the cells are at the time of transplantation, the greater the risk of neural overgrowth (Elkabetz et al., 2008), so the stage of neural differentiation and the expected amount of proliferation would have to be very precisely controlled and accounted for. Although progress is being made on elucidating the transcriptional regulation of fate specification of cortical excitatory neurons (Table 2) (Arlotta et al., 2005, Leone et al., 2008 and Molyneaux et al., 2009), little is known about the molecular mechanisms that govern which subtype of cortical neuron is produced by a radial glial (RG) cell division at different times during neurogenesis (Figure 1D). Here, we will focus on the feasibility of producing a single subtype of neuron from progenitor cells that are programmed to produce several cell types in a defined sequence.