Genetic and developmental models for the neural control of breathing in vertebrates

The present paper reviews some of the possible mechanisms that may link gene function in the brainstem and breathing patterns in vertebrates. On one hand, adaptation and acclimatisation of mature breathing to environmental constraints such as hypoxia, involves complex regulation of the gene expression in precise cardiorespiratory sites of the brainstem. On the other hand, targeted inactivation of different genes suggests that postnatal respiratory variables at rest depend on genes controlling the prenatal development of the brainstem. During embryogenesis, neurotrophins (gdnf, bdnf) regulate the survival of specific cellular populations composing the respiratory neuronal network. The expression of developmental genes such as Hox and Krox-20 initiates hindbrain segmentation, the earliest sign of regionalisation in the brainstem. As shown in the chick embryo, segmental specifications allow the establishment of an active embryonic rhythmic network and later insertion of specific neuronal circuits increasing the primordial rhythm frequency to near mature values.