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The coordinated spatial and temporal control of neuronal fate determination. Shown here is the expression of the motor neuron (MN) marker Isl1 (blue), the Serotonergic (S) neuron marker Pet1 (green), and Hoxb1 (red) in the mouse hindbrain at embryonic day 11.5 (E11.5). MNs and S neurons are sequentially generated from a common pool of ventral progenitor cells at all levels of the hindbrain except in rhombomere 4 (marked by Hoxb1 expression). At this axial level, the period of MN generation is extended and S neurons are suppressed. The timing of MN and S neuron generation in the hindbrain critically depends on the integrated activities of Nkx and Hox class homeodomain proteins. A primary role of these proteins is to coordinate the spatial and temporal activation of the homeodomain protein Phox2b, which in turn acts as a temporal switch in the selection of MN or S neuronal fate. (At E11.5, S neurons are still positioned close to the ventral midline, whereas early-born MNs at this stage have migrated to occupy a more lateral position of neural tube.) (For details, see Pattyn et al., p. 729.)