Hes1 and Hes5 are required for differentiation of pituicytes and formation of the neurohypophysis in pituitary development.
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.
Department of Neurosurgery, Kyoto University Graduate School of Medicine, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan; Institute for Virus Research, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
Masanori
M
Goto
Department of Neurosurgery, Kyoto University Graduate School of Medicine, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan; Department of Neurosurgery, Shiga Medical Center for Adults, 5-4-30 Moriyama, Moriyama, Shiga 524-8524, Japan. Electronic address: mhojo@kuhp.kyoto-u.ac.jp.
Masato
M
Hojo
Department of Neurosurgery, Kyoto University Graduate School of Medicine, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan; Institute for Virus Research, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
Mitsushige
M
Ando
Department of Neurosurgery, Kyoto University Graduate School of Medicine, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan; Institute for Virus Research, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
Aya
A
Kita
Department of Neurosurgery, Kyoto University Graduate School of Medicine, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan; Institute for Virus Research, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
Masashi
M
Kitagawa
Institute for Virus Research, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
Toshiyuki
T
Ohtsuka
Institute for Virus Research, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
Ryoichiro
R
Kageyama
Department of Neurosurgery, Kyoto University Graduate School of Medicine, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
Susumu
S
Miyamoto
D000818:Animals; D000831:Animals, Newborn; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D001973:Bromodeoxyuridine / Q000378:metabolism; D064026:Calbindins / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics*; D049109:Cell Proliferation; D004622:Embryo, Mammalian; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D019394:Ki-67 Antigen / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010902:Pituitary Gland / Q000166:cytology / Q000196:embryology / Q000254:growth & development; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D055748:SOXB1 Transcription Factors / Q000378:metabolism; D013234:Stem Cells / Q000378:metabolism; D000072056:Transcription Factor HES-1; D014404:Tubulin / Q000378:metabolism; D014667:Vasopressins / Q000378:metabolism
D051792:Basic Helix-Loop-Helix Proteins; D001973:Bromodeoxyuridine; D064026:Calbindins; D018398:Homeodomain Proteins; D019394:Ki-67 Antigen; D018168:Receptors, Retinoic Acid; D012097:Repressor Proteins; D055748:SOXB1 Transcription Factors; D000072056:Transcription Factor HES-1; D014404:Tubulin; D014667:Vasopressins; C489734:Hes1 protein, mouse; C489685:Hes5 protein, mouse; C527783:Sox2 protein, mouse; C462941:beta3 tubulin, mouse; C082928:retinoic acid binding protein II, cellular
Hes1; Hes5; Neurohypophysis; Pituicyte; Pituitary development