Regulation of respiratory neuron development by neurotrophic and transcriptional signaling mechanisms.

Functionally diverse populations of respiratory neurons appear to be targets of common neurotrophic and transcriptional signaling pathways. For example, peripheral chemoafferent neurons and noradrenergic neurons in the pontine A5 cell group both require co-signaling by brain derived neurotrophic factor (BDNF) and glial cell line derived neurotrophic factor (GDNF) for survival, growth and/or phenotypic differentiation. Moreover, these same cell groups are dependent on the Phox2 family of transcription factors for early cell type specification. In addition, BDNF and its receptor, TrkB, are expressed in the pre-Botzinger complex (pBC), a critical site for respiratory rhythm generation, and exogenous BDNF can modulate the activity of pBC neurons. This convergence of BDNF, GDNF and Phox2 dependencies may help to explain how mutations in each of these pathways can result in human developmental disorders of breathing.