FGF AND SHH SIGNALS CONTROL DOPAMINERGIC AND SEROTONERGIC CELL FATE IN THE ANTERIOR NEURAL PLATE

During development, distinct classes of neurons are specified in preci se locations along the dorso-ventral and anterior-posterior axes of th e neural tube. We provide evidence that intersections of Shh, which is expressed along the ventral neural tube, and FGF8, which is locally p roduced at the mid/hindbrain boundary and in the rostral forebrain, cr eate induction sites for dopaminergic neurons in the midbrain and fore brain. The same intersection, when preceded by a third signal, FGF4, w hich is expressed in the primitive streak, defines an inductive center for hindbrain 5-HT neurons. These findings illustrate that cell patte rning in the neural plate is a multistep process in which early induce rs, which initially divide the neural plate into crude compartments, a re replaced by multiple local organizing centers, which specify distin ct neuronal cell types within these compartments.