TanyCilia · The role of tanycytic cilia in hypothalamic functions.

Obesity and metabolic diseases are a top priority challenge for health systems. Monitoring changes in the bodys energy levels is a task of the hypothalamus (HpT) which integrates the actions of peripheral hormones and nutrients with neural information. However, this regulation is complex, and the causes and biological mechanisms leading to metabolic disorders remain to be explored. Among the cells involved, tanycytes play a key role. They are glial cells that line the third ventricle and mediate information about changes in the circulation to various HpT nuclei. They regulate important neuroendocrine functions such as food intake and energy balance. Although tanycytes are known to integrate external and internal signals, the specific cellular organelles through which they sense these cues remain unknown. Primary cilia (PC) are one such compartment crucial for perceiving peripheral signals, and they are indeed present in tanycytes. We have coined the name tanycilia for them. However, the function of tanycilia is still unclear. Here, we hypothesize that cilia may act as antennae for tanycytes, sensing nutrients or hormones, enabling adaptive cellular responses, and transmitting metabolic information to neurons. This project aims to I) characterize tanycilia morphology for the first time; II) identify their functions, primarily in the regulation of metabolism; and III) examine them in pathological contexts like obesity and anorexia. To achieve these goals, we will employ immunohistochemical techniques to characterize tanycilia in wild-type mice. To investigate their function, we will genetically manipulate tanycilia using inducible mouse models in combination with tanycyte-specific adeno-associated viruses (rAAV). The discovery of tanycilia's roles in integrating peripheral signals to regulate neuroendocrine functions holds promise for understanding and treating metabolic disorders.