Developmental gene control of brainstem function: views from the embryo.

The respiratory rhythm is generated within the hindbrain reticular formation, rostrally in the vicinity of the facial nucleus and caudally within the vagal/glossopharyngeal domain. This is probably one of the best models to understand how genes have been selected and conserved to control adaptive behaviour in vertebrates. The para-facial region is well understood with respect to the transcription factors that underlie antero-posterior specification of neural progenitors in the embryo. Hox paralogs and Hox-regulating genes kreisler and Krox-20 govern transient formation of developmental compartments, the rhombomeres, in which rhythmic neuronal networks develop. Hox are master genes selecting and coordinating the developmental fate of reticular and motor neurons thereby specifying patterns of motor activities operating throughout life. Neuronal function and development are also tightly linked in the vagal/glossopharyngeal domain. At this level, bdnf acts as a neurotrophin of peripheral chemoafferent neural populations and as a neuromodulator of the central rhythmogenic respiratory circuits. A general view is now emerging on the role of developmental transcription and trophic factors allowing the coordinated integration of different neuronal types to produce, and eventually refine, respiratory rhythmic pattern in a use-dependent manner.