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Figure 2


Fig. 2. Postmitotic TTFs in Drosophila and mammals. (A) In Drosophila, wild-type (wt) mushroom body (MB) neuroblasts (large circles) generate MB neurons (small circles). Early-born MB neurons express high levels of the transcription factor Chinmo (dark blue), whereas later-born MB neurons express either low levels (light blue) or none (white). Postmitotic levels of Chinmo specify the different temporal identities of {gamma}, {alpha}'/β', p{alpha}/β or {alpha}/β neurons. A decrease in Chinmo expression (Chinmo-) leads to fewer {gamma} neurons and to the precocious generation of supernumerary p{alpha}/β neurons. Chinmo does not appear to specify the temporal identity of {alpha}/β neurons. If high levels of Chinmo are maintained in all postmitotic neurons (+ Chinmo), the early temporal identity ({gamma}) is continuously generated at the expense of all later temporal identities ({alpha}'/β', p{alpha}/β and {alpha}/β). (B) (a) In the mouse cerebral cortex, multipotent progenitors (mP) generate two distinct pools of progenitors: deep-layer progenitors (dP) and superficial-layer progenitors (sP). In turn, dP and sP sequentially generate the different neuronal subtypes (coloured circles) that are associated with deep (SP/VI/V) and superficial (IV/III/II) cortical layers, respectively. Postmitotic projection neurons of the different layers express different combinations of Sox5 (SRY-box 5), Ctip2 (Coup-TF-interacting protein 2) and Satb2 (special AT-rich sequence binding protein 2). Sox5 is normally expressed at different levels in the neurons of each of the layers SP, VI and V. (b) Sox5 inactivation leads to a reduction in the sub-plate (SP) neuronal layer. SP neurons appear to be replaced by ectopic Ctip2+ neurons (yellow), characteristic of layer V. For clarity, ectopic Ctip2+ neurons located in superficial layers IV/III/II have been omitted as their origin is unclear. Inactivation of Satb2, which is predominantly expressed by layer IV/III/II neurons, leads to these late-born neurons acquiring an earlier Ctip2+ identity. (c) Sox5 and Satb2 repress Ctip2, and biochemical studies suggest that the Satb2 repression is direct (Alcamo et al., 2008; Britanova et al., 2008). As Ctip2 and Satb2 are transiently coexpressed by some layer V neurons (Alcamo et al., 2008), it might be that a stable layer-specific cell identity is only acquired sometime after neurons become postmitotic.