Methodological Challenges for Ablation of BMPR1A in Hypothalamic Tanycytes-A Cautionary Tale.

The hypothalamus coordinates energy-balance regulation and is also a neurogenic/plastic region in the adult brain. Tanycytes, a specialized population of radial glial-like cells lining the third ventricle, reside at the critical interface between the blood, cerebrospinal fluid, and hypothalamic parenchyma. This unique positioning enables them to sense metabolic and nutrient-derived signals, and to shuttle molecules between periphery and brain. Tanycytes can respond to glucose and lipids, as demonstrated by a calcium transient down their long processes that extend into the hypothalamic nuclei. Tanycytes are also capable of self-renewal and differentiation after brain injury, supporting their classification as putative neural stem cells in the adult hypothalamus. Bone morphogenetic protein (BMP) signaling regulates neuroplasticity and contributes to metabolic regulation, including appetite and sympathetic drive to adipose. We previously demonstrated that central administration of BMP7 suppresses appetite, and BMP receptor 1A (BMPR1A) in anorectic hypothalamic POMC neurons impacts appetite regulation. BMPR1A is also tightly and highly co-expressed in hypothalamic tanycytes. Here, we attempted to genetically inactivate BMPR1A in adult tanycytes to explore its functional roles. Using the Rax-CreER