Research ReportHes1 and Hes5 are required for differentiation of pituicytes and formation of the neurohypophysis in pituitary development

•In Hes mutant embryos, the ventral diencephalon fails to evaginate.•In addition, progenitors differentiate into neurons at the expense of pituicytes.•The proliferative zone is located at the base of the infundibulum.•Progenitors of pituicytes may be regulated by the gliogenic activity of Hes genes.

The pituitary gland is a critical endocrine organ regulating diverse physiological functions, including homeostasis, metabolism, reproduction, and growth. It is composed of two distinct entities: the adenohypophysis, including the anterior and intermediate lobes, and the neurohypophysis known as the posterior lobe. The neurohypophysis is composed of pituicytes (glial cells) and axons projected from hypothalamic neurons. The adenohypophysis derives from Rathke's pouch, whereas the neurohypophysis derives from the infundibulum, an evagination of the ventral diencephalon. Molecular mechanisms of adenohypophysis development are much better understood, but little is known about mechanisms that regulate neurohypophysis development. Hes genes, known as Notch effectors, play a crucial role in specifying cellular fates during the development of various tissues and organs. Here, we report that the ventral diencephalon fails to evaginate resulting in complete loss of the posterior pituitary lobe in Hes1−/−; Hes5+/− mutant embryos. In these mutant mice, progenitor cells are differentiated into neurons at the expense of pituicytes in the ventral diencephalon. In the developing neurohypophysis, the proliferative zone is located at the base of the infundibulum. Thus, Hes1 and Hes5 modulate not only maintenance of progenitor cells but also pituicyte versus neuron fate specification during neurohypophysis development.