Project 3

Subcellular characterization of tanycyte biology

In the hypothalamus, elongated glial cells called tanycytes line the walls and floor of the third ventricle and extend their processes into the brain parenchyma up to brain blood vessels. Their peculiar morphology allows tanycytes to detect signals about the metabolic state, in the cerebrospinal fluid and the blood, and interact with numerous neural cells, including neurons. However, many questions remain regarding the molecular mechanisms underlying tanycyte/neuron communication for energy balance regulation. One of the most intriguing questions for us is how tanycytes can communicate with different neuronal populations when adapting to changing nutritional conditions.

Tanycytes show a fantastic ultrastructure highlighting the possibility of diverse communication mechanisms. For example, tanycytes form contacts with arcuate nucleus (ARH) neurons through spines, swellings, and boutons (Pasquettaz et al. 2021). They contain a rich and heterogenous vesicular system including single-membrane vesicles, double-membrane vesicles, multivesicular bodies, multivesicular cargoes, and dense-core vesicles (Pasquettaz et al. 2021). Additionally, subcellular components like the endoplasmic reticulum, ribosomes, and even mRNAs are present from their cell bodies down to their endfeet, drawing attention to local translation as a potential plasticity mechanism of tanycytes (Pasquettaz et al. 2021). Finally, studies have shown the existence of physical and functional tanycytic networks that sustain the firing activity of ARH neurons (Lhomme et al. 2021), and that tanycyte calcium transients are necessary for this communication (Bolborea et al. 2020).

Using a multidisciplinary approach, we take advantage of both in vivo and in vitro models to elucidate the interplay of different cellular compartments and their role in tanycyte-neuron communication in different nutritional contexts.

Under construction