Premium
Characterisation of endogenous players in fibroblast growth factor‐regulated functions of hypothalamic tanycytes and energy‐balance nuclei
Author(s) -
Kaminskas Benediktas,
Goodman Timothy,
Hagan Andrew,
Bellusci Saverio,
Ornitz David M.,
Hajihosseini Mohammad K.
Publication year - 2019
Publication title -
journal of neuroendocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.062
H-Index - 116
eISSN - 1365-2826
pISSN - 0953-8194
DOI - 10.1111/jne.12750
Subject(s) - intracrine , fibroblast growth factor , biology , endocrinology , medicine , fibroblast growth factor receptor , hypothalamus , endogeny , energy homeostasis , microbiology and biotechnology , receptor , autocrine signalling , obesity
The mammalian hypothalamus regulates key homeostatic and neuroendocrine functions ranging from circadian rhythm and energy balance to growth and reproductive cycles via the hypothalamic‐pituitary and hypothalamic‐thyroid axes. In addition to its neurones, tanycytes are taking centre stage in the short‐ and long‐term augmentation and integration of diverse hypothalamic functions, although the genetic regulators and mediators of their involvement are poorly understood. Exogenous interventions have implicated fibroblast growth factor ( FGF ) signalling, although the focal point of the action of FGF 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 hybridisation, immunolabelling and transgenic reporter mice, aiming to map their spatial distribution in the adult hypothalamus. Our findings suggest that β‐tanycytes are the likely focal point of exogenous and endogenous action of FGF in the third ventricular wall, utilising FGF receptor ( FGFR )1 and FGFR 2 III c isoforms, but not FGFR 3. Key III c‐activating endogenous ligands include FGF 1, 2, 9 and 18, which are expressed by a subset of ependymal and parenchymal cells. In the parenchymal compartment, FGFR 1‐3 show divergent patterns, with FGFR 1 being predominant in neuronal nuclei and expression of FGFR 3 being associated with glial cell function. Intracrine FGF s are also present, suggestive of multiple modes of FGF function. Our findings provide a testable framework for understanding the complex role of FGF s with respect to regulating the metabolic endocrine and neurogenic functions of hypothalamus in vivo.