Characterization of endogenous players in Fibroblast Growth Factor‐regulated functions of hypothalamic tanycytes and energy‐balance nuclei

Benediktas Kaminskas, Timothy Goodman, Andrew Hagan, Saverio Bellusci, David M. Ornitz, Mohammad K. Hajihosseini

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The mammalian hypothalamus regulates key homeostatic and neuroendocrine functions ranging from circadian rhythm and energy‐balance to growth and reproductive cycles via the hypothalamo‐pituitary and hypothalamo‐thyroid axes. In addition to its neurons, tanycytes are taking centre stage in the short and long term augmentation and integration of diverse hypothalamic functions, but the genetic regulators and mediators of their involvement are poorly understood. Exogenous interventions have implicated Fibroblast growth factor (FGF) signalling, but the focal point of FGF action and any role for putative endogenous players also remains elusive. We carried out a comprehensive high‐resolution screen of FGF signalling pathway mediators and modifiers using a combination of in situ hybridization, immunolabelling and transgenic reporter mice, to map their spatial distribution in the adult hypothalamus. Our findings suggest that beta tanycytes are the likely focal point of exogenous and endogenous FGF action in the third ventricular wall, utilising FGF‐receptors (FGFRs) ‐1 and ‐2 IIIc isoforms, but not FGFR3. Key IIIc‐activating endogenous ligands include FGFs 1, 2, 9 and 18, which are expressed by a subset of ependymal and parenchymal cells. In the parenchymal compartment, FGFRs 1‐3 show divergent patterns, with FGFR1 predominant in neuronal nuclei and FGFR3 expression being associated with glial cell function. Intracrine FGFs are also present, suggestive of multiple modes of FGF function. Our findings provide a testable framework for understanding the complex role of FGFs in regulating the metabolic endocrine and neurogenic functions of hypothalamus in vivo.
Original languageEnglish
Article numbere12750
JournalJournal of Neuroendocrinology
Issue number8
Early online date20 May 2019
Publication statusPublished - Aug 2019

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