Semaphorins in the development, homeostasis and disease of hormone systems

Semaphorin proteins are among the best-studied families of guidance cues. Initially characterized as repulsive neuronal guidance cues, during the last decade, significant progress has been made in defining their involvement in the regulation of dynamic changes in the cellular cytoskeleton during embryonic and postnatal neuronal development, under both physiological and pathological conditions. However, semaphorins are not restricted to the nervous system but widely expressed in other tissues, where they play key roles in angiogenesis and organogenesis.In recent years, there has been an increasing emphasis on the potential influence of semaphorins on the development and homeostasis of hormone systems, and conversely, how circulating reproductive hormones regulate semaphorin expression. In this review, we summarize recent studies analyzing the contribution of semaphorin signaling to the morphogenesis, differentiation and plasticity of fundamental neuroendocrine and endocrine systems that regulate key physiological processes, such as reproduction, bone formation and the control of energy homeostasis.

► Semaphorin signaling imparts guidance information to migrating GnRH cells during development.
► Semaphorin 3A is mutated in a human form of reproductive insufficiency.
► Semaphorin signaling regulates key physiological processes during adulthood.