8037 Ciliopathy Genes are Expressed in the Developing Pituitary Gland and Mature Hormone-Producing Cells

Abstract Disclosure: S.W. Athul: None. N. Jaramillo: None. B.S. Ellsworth: None. Primary cilia play critical roles in several signaling pathways including sonic hedgehog and Wnt to help regulate cell differentiation and proliferation. Ciliopathies are a group of disorders associated with genetic mutations resulting in an abnormal formation or structure of the primary cilium. Recently, congenital hypopituitarism was identified in some patients with ciliopathies. To begin to evaluate the role of these genes in pituitary gland function, we used the International Mouse Phenotyping Consortium (IMPC) database to identify several ciliopathy genes that, when mutated, cause pituitary hypoplasia in mice. To determine if primary cilia are present in the somatotrope-like GHFT1-5 cells, ARL13B, a regulatory GTPase protein that is localized to the ciliary membrane, was identified. In the absence of serum, it was seen that the number of cilia present was relatively high, likely as a result of the lower rate of cell division. Gene expression of the ciliopathy genes, Cc2d2a, Mks1, and Pibf1 was detected via RT-qPCR in GHFT1-5 cells. While Mks1 and Pibf1 were expressed at low levels, Cc2d2a was more robustly expressed. Expression of Cc2d2a, Mks1, Pibf1, and Rpgrip1l was observed on adult pituitary glands of C57BL/6 mice. Consistent with active SHH signaling during early pituitary organogenesis we see the expression of Rpgrip1l and Pibf1 in Rathke’s pouch at e10.5, 11.5, and e12.5. ARL13B and α-Tubulin, markers of primary cilia, were used to determine which hormone-producing cell types contain primary cilia in adult and e18.5 C57BL/6 mice. Primary cilia are present in a fraction of all hormone-producing cell types. These studies suggest that primary cilia are present in the pituitary gland during early organogenesis and may also be involved in the function of mature hormone-producing cells. Understanding the function of ciliopathy genes is important for expanding our understanding of congenital hypopituitarism. Presentation: 6/3/2024