Role of Phox2b in assembly of the circuits of the autonomic nervous system

The wiring of the brain, the way in which vast numbers of neuronal types are produced, migrate and grow neurites in precise spatial arrangements and connect to their proper target, and the prominent role of transcription factors in these phenomena still represent major questions in neurobiology. Using the reflex circuits of the autonomic nervous system of vertebrates and their master transcription regulator the homeodomain protein Phox2b as a model we explored this issue from several angles. From a molecular point of view we have shown that Phox2b is required in visceral neurons after it has specified them, providing one of the first examples for a “terminal selector gene” in vertebrates. From a cellular point of view we uncovered a novel mechanism for circuit building, whereby some visceral neurons direct the migration and axonal guidance of others in the visceral circuit of the facial nerve. In neuroanatomical terms, this amounts to an intriguing case of self-assembly of a reflex circuit, whereby its afferent pathway (specialized in taste reception) instructs the development of its efferent pathway (that vasodilates blood vessels of the mouth and stimulates salivatory glands). We are currently testing the generalities of this self-assembly mechanism, to further explore the role of Phox2b as determinant of connectivity of the visceral nervous system.