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Figure 3


Fig. 3. Candidate progenitor TTFs in vertebrates. (A) (a) In most rhombomeres (r) of wild-type (wt) mouse and chick hindbrains, ventral progenitors (large circles) express Phox2b (Px2b) early and then Foxa2 (Fxa2) later, correspondingly generating VM (yellow) then 5HT (red) neurons. In Phox2b-/- mice, progenitors express Foxa2 and generate 5HT neurons precociously. In Foxa2-/- mice, VM generation is prolonged. (b) Loss- and gain-of-function experiments show that it is sequential cross-repression that promotes the switch between the VM and 5HT neuronal identities. (c) Hoxb1 (Hxb1) expression in r4 maintains Phox2b expression, thus preventing the switch to 5HT neurogenesis in this particular segment of the hindbrain. (B) (a) In the spinal cord, two types of progenitors (1 and 2) first generate neurons then glia. One progenitor type generates V2 interneurons (V2) and then astrocytes (a) and the other generates motoneurons (MN) and then oligodendrocytes (o). The lineage-specific factors Scl and Olig2, acting in combination with the temporal factor Sox9, influence whether an astrocytic or an oligodendrocytic cell identity is specified. (b) Loss of Sox9 activity in either progenitor type appears to prevent the neuronal-to-glial switch. (c) The orphan nuclear receptors Coup-TFI/II are transiently expressed in early neural progenitors and appear to act as switching factors as their knockdown prevents the switch from neurons (n) to glia (g). (C)(a) Cortical progenitors (large circles) can sequentially generate different neuronal subtypes (small coloured circles) during mouse embryogenesis that are each associated with different layers (SP, VI, V or IV/III/II). Fezf2 (Fzf2) is expressed in progenitors at the time they generate neurons that colonise layers VI and V. (b) Misexpression (red text) of Fezf2 during late stages of corticogenesis forces late progenitors to generate Ctip2+ neurons (yellow) typical of layer V. Fezf2 inactivation results in an excess of Satb2+ neurons (green), typical of superficial layers IV/III/II, at the expense of layer VI and V neurons.





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