Endocrine Abstracts

The FGF signalling pathway regulates cell proliferation, differentiation, migration and cell specification in mutliple developing and adult tissues. It has also been implicated in tumor development and progression with a significant role in the cancer pathobiology of several malignant tumors including melanoma, breast, pancreas, head and neck and non-small lung cell cancer. FGF signalling plays a major role in the postnatal hypothalamic-pituitary (HP) axis, with dysregulation of FGF pathway components, including FGF1, FGF8 and FGFR1, linked to disorders including Kallmann syndrome, septo-optic dysplasia and congenital hypopituitarism. FGF8 and FGF10 expressed by the ventral diencephalon are required for proper development and expansion of Rathke’s pouch, with early loss of Rathke’s pouch in FGF10 null mutant mice. In the hypothalamus, FGF10 promotes the maintenance of tanycytes in an uncommitted state, suppressing neurogenic differentiation. To conduct an in-depth analysis of the expression of Fgf genes and their receptors across the different cell types of the anterior pituitary gland, we have computationally mined published single cell sequencing data of the murine postnatal gland. We present the heterogenous expression of FGF pathway components including ligands, receptors and targets. Notably, Fgf10 is expressed by multiple Rathke’s pouch derivatives in the postnatal pituitary, including subsets of stem cells, lineage-committed progenitors and hormone producing cells. We have validated these findings in mice expressing beta-galactosidase under the control of the Fgf10 promoter (Fgf10-LacZ), through immunofluorescence analyses at different postnatal stages. Additionally, using CellChat DB computational analysis, we have identified that anterior pituitary stem cells signal to other committed populations in the gland through FGF1-FGFR1 ligand-receptor interactions. The complete validation of our computational data will provide new insights about the specific roles of FGF signalling members in the maintenance and regulation of the anterior pituitary cell compartments.