Fgf8 regulation of parasympathetic postganglionic neuron development
The cranial parasympathetic reflex circuit contains sensory, pre- and postganglionic neurons. How this circuit is wired and the cues that control this process are unknown. We discovered that the fate of neural crest (NC)-derived postganglionic (PG) neurons depends on interaction with complementary placode-derived sensory ganglia. We show that the expression of Fgf8 in the head is strategically poised to control this cellular relationship. Loss of Fgf8 globally leads to an early loss of placodal ganglia and reduced number of PG neurons. The latter finding is associated with the early loss of NC by apoptosis. This loss occurs concurrent with the interaction between the NC and placodal ganglia. Analyses of tissue-specific loss of Fgf8 show that Fgf8 regulates the differentiation of PG neurons by different mechanisms. For example, mesodermal Fgf8 deficiency leads to a loss in PG neurons that is independent of NC apoptosis or defects in placodal ganglia, but dependent on early differentiation of PG precursors. Ectodermal Fgf8 deficiency also causes a reduction of PG neurons. However, the mechanism occurs through regulating early proliferation and later differentiation of PG precursors. Loss of PG neurons is a consequence of Fgf8 from mesoderm and ectoderm binding to Fgf receptors on the NC, requiring both Fgfr1 and Fgfr2. Finally, we show that the interaction of NC and placodal cells is not hard-wired, but plastic along the anterior-posterior axis. Our findings provide a general principle by which the formation of the parasympathetic circuit depends on the interaction of its precursors and fgf8 signals.