Cortical excitatory projection neurons are generated from the ventricular and subventricular zones in defined periods. Their precursors migrate and settle in distinct cortical layers in an inside-out manner [50]. Cajal-Retzius neurons occupying the marginal zone are born first, followed by corticothalamic neurons at layer VI and callosal and subcerebral projection neurons at layer V, and later layer IV and layer II/III pyramidal neurons [51]. Neurons in each cortical layer or areal (motor, somatosensory and visual) are endowed with specific marker expressions [51]. We and others have noticed Tbr1 expression in a fraction of the iN cells, indicating potential region-specific features of cortical (preplate and layer 6), olfactory bulb and eminentia thalami neurons [52]. Given the diversity of neocortical neurons, more cortical areal and layer specific markers have to be used to better define the iN cells generated. While mouse iN cells appeared of exclusive central nervous system identity, a fraction of the human fibroblast-derived iN cells expressed peripherin, a neuronal marker of the peripheral nervous system [53]. How the same combination of transcription factors can give rise to iN cells with features of the central and peripheral nervous systems remains to be addressed.
