FGF and Shh Signals Control Dopaminergic and Serotonergic Cell Fate in the Anterior Neural Plate

During development, distinct classes of neurons are specified in precise locations along the dorso-ventral and anterior-posterior axes of the neural tube. We provide evidence that intersections of Shh, which is expressed along the ventral neural tube, and FGF8, which is locally produced at the mid/hindbrain boundary and in the rostral forebrain, create induction sites for dopaminergic neurons in the midbrain and forebrain. The same intersection, when preceded by a third signal, FGF4, which is expressed in the primitive streak, defines an inductive center for hindbrain 5-HT neurons. These findings illustrate that cell patterning in the neural plate is a multistep process in which early inducers, which initially divide the neural plate into crude compartments, are replaced by multiple local organizing centers, which specify distinct neuronal cell types within these compartments.