Neuronal growth factors and development of respiratory control

Neurotrophic molecules, released by neurons and neural target tissues, play a pivotal role in regulating neuronal development and plasticity. This article reviews recent work demonstrating the pivotal role of two such molecules, brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF), in the growth and maturation of respiratory neurons and the expression of normal ventilatory behavior. Although BDNF and GDNF are structurally dissimilar and signal through wholly distinct receptors, they are both required for development of peripheral chemoafferent neurons that provide hypoxic drive to the brainstem respiratory network. Studies of genetically engineered mice carrying targeted deletions in the genes encoding BDNF and GDNF, as well as genetic linkage analysis in humans, indicate that these trophic molecules may be candidate genes for human developmental disorders of breathing.