Early Development of the Pituitary Gland: Induction and Shaping of Rathke’s Pouch

2005 ◽  
Vol 6 (3) ◽  
pp. 161-172 ◽  
Author(s):  
Karine Rizzoti ◽  
Robin Lovell-Badge
Keyword(s):  
Pituitary Gland ◽  
Early Development ◽  
Rathke’S Pouch ◽  
Rathke's Pouch

scholarly journals Role of PROP1 in Pituitary Gland Growth

2005 ◽  
Vol 19 (3) ◽  
pp. 698-710 ◽  
Author(s):  
Robert D. Ward ◽  
Lori T. Raetzman ◽  
Hoonkyo Suh ◽  
Brandon M. Stone ◽  
Igor O. Nasonkin ◽  
...  
Keyword(s):  
Pituitary Gland ◽  
Anterior Pituitary ◽  
Anterior Lobe ◽  
Clinical Findings ◽  
Proliferative Potential ◽  
Rathke’S Pouch ◽  
Rathke's Pouch ◽  
Pituitary Hyperplasia ◽  
Dividing Cells ◽  
Pituitary Hypoplasia

Abstract Mutations in the PROP1 transcription factor gene lead to reduced production of thyrotropin, GH, prolactin, and gonadotropins as well as to pituitary hypoplasia in adult humans and mice. Some PROP1-deficient patients initially exhibit pituitary hyperplasia that resolves to hypoplasia. To understand this feature and to explore the mechanism whereby PROP1 regulates anterior pituitary gland growth, we carried out longitudinal studies in normal and Prop1-deficient dwarf mice from early embryogenesis through adulthood, examining the volume of Rathke’s pouch and its derivatives, the position and number of dividing cells, the rate of apoptosis, and cell migration by pulse labeling. The results suggest that anterior pituitary progenitors normally leave the perilumenal region of Rathke’s pouch and migrate to form the anterior lobe as they differentiate. Some of the cells that seed the anterior lobe during organogenesis have proliferative potential, supporting the expansion of the anterior lobe after birth. Prop1-deficient fetal pituitaries are dysmorphic because mutant cells are retained in the perilumenal area and fail to differentiate. After birth, mutant pituitaries exhibit enhanced apoptosis and reduced proliferation, apparently because the mutant anterior lobe is not seeded with progenitors. These studies suggest a mechanism for Prop1 action and an explanation for some of the clinical findings in human patients.

scholarly journals SAT-288 Pituitary Developmental Defects Caused by Haploinsufficiency for the Transcription Factor SIX3 Are Worsened by POU1F1 Deficiency

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Michelle Brinkmeier ◽  
Sally Ann Camper
Keyword(s):  
Transcription Factor ◽  
Pituitary Gland ◽  
Clinical Features ◽  
Hormone Deficiency ◽  
Pituitary Hormone ◽  
Loss Of Function ◽  
Pituitary Hormone Deficiency ◽  
Rathke’S Pouch ◽  
Rathke's Pouch ◽  
Vasopressin Neurons

Abstract Advances in genomic technologies are revolutionizing the practice of medicine by delivering molecular diagnoses that can be informative for prognosis and treatment of genetic disorders. Most of the known genetic causes of multiple pituitary hormone deficiency have been investigated as monogenic disorders. It can be challenging to predict clinical features from genetic data, as loss of function mutations in some genes can present with a spectrum of phenotypes ranging from craniofacial abnormalities, intellectual disability, and neurosensory and neuroendocrine defects to pituitary hormone deficiency with no other abnormalities. Although maternal exposures could be contributing factors, the contribution of rare, deleterious variation in other genes is a likely contributor. In humans, loss of function mutations in the transcription factor SIX3 cause variable, autosomal dominant holoprosencephaly with incomplete penetrance, and mouse models recapitulate some of the clinical features. Because Six3 and Pou1f1 gene expression patterns overlap in pituitary development, we hypothesized that doubly heterozygous mice (Six3+/-; Pou1f1+/dw) might have pituitary anomalies not present in singly heterozygous mice. We intercrossed Six3+/- and Pou1f1+/dw mice to produce doubly heterozygous animals. At e11.5, both Six3+/- and Six3+/-; Pou1f1+/dw exhibited abnormal morphology of the developing infundibulum and Rathke’s pouch, although ventral diencephalon expression of Tle4, Fgf10, and Nkx2.1 appeared normal. Both newborn Six3+/- and Six3+/-; Pou1f1+/dw littermates had abnormal pituitary gland morphology that resembled that of Aes-/-. AES is a co-repressor that interacts with SIX3. Specification of vasopressin neurons and anterior lobe hormone cell types appeared normal. Mice of all genotypes were born in expected Mendelian ratios (N=144, p=0.49), and there were no significant differences in body weight at 3 wks. A portion of the Six3+/- and doubly heterozygous mice developed hydrocephalus, exhibited failure to thrive, and died (6-9% of N=82, 85, respectively). At 6 wks, 25% (N=61) of the Six3+/-; Pou1f1+/dw animals exhibited striking pituitary dysmorphology in which the rostral aspect of the pituitary penetrated the palate. This was not observed in single heterozygotes. These results reveal that haploinsufficiency for Six3 affects Rathke’s pouch formation, resulting in pituitary gland dysmorphology in and around the stem cell niche. A significant portion of the Six3+/-; Pou1f1+/dw doubly heterozygous mice have a more pronounced pituitary phenotype than Six3+/-, supporting the possibility of digenic pituitary disease and highlighting phenotypic variability. Genetically engineered mice provide an excellent tool for assessing the possibility of gene-gene interactions that could enhance the severity of hypopituitarism and associated craniofacial development.

Hedgehog signaling is required for pituitary gland development

Development ◽  
2001 ◽  
Vol 128 (3) ◽  
pp. 377-386 ◽  
Author(s):  
M. Treier ◽  
S. O'Connell ◽  
A. Gleiberman ◽  
J. Price ◽  
D.P. Szeto ◽  
...  
Keyword(s):  
Pituitary Gland ◽  
Hedgehog Signaling ◽  
Homeobox Gene ◽  
Cell Types ◽  
Oral Epithelium ◽  
Regulatory Sequences ◽  
Rathke’S Pouch ◽  
Rathke's Pouch ◽  
Oral Ectoderm ◽  
Gland Development

Pituitary gland development serves as an excellent model system in which to study the emergence of distinct cell types from a common primordium in mammalian organogenesis. We have investigated the role of the morphogen Sonic hedgehog (SHH) in outgrowth and differentiation of the pituitary gland using loss- and gain-of-function studies in transgenic mice. Shh is expressed throughout the ventral diencephalon and the oral ectoderm, but its expression is subsequently absent from the nascent Rathke's pouch as soon as it becomes morphologically visible, creating a Shh boundary within the oral epithelium. We used oral ectoderm/Rathke's pouch-specific 5′ regulatory sequences (Pitx1(HS)) from the bicoid related pituitary homeobox gene (Pitx1) to target overexpression of the Hedgehog inhibitor Hip (Huntingtin interacting protein) to block Hedgehog signaling, finding that SHH is required for proliferation of the pituitary gland. In addition, we provide evidence that Hedgehog signaling, acting at the Shh boundary within the oral ectoderm, may exert a role in differentiation of ventral cell types (gonadotropes and thyrotropes) by inducing Bmp2 expression in Rathke's pouch, which subsequently regulates expression of ventral transcription factors, particularly Gata2. Furthermore, our data suggest that Hedgehog signaling, together with FGF8/10 signaling, synergizes to regulate expression of the LIM homeobox gene Lhx3, which has been proved to be essential for initial pituitary gland formation. Thus, SHH appears to exert effects on both proliferation and cell-type determination in pituitary gland development.

scholarly journals SIX3 Variant Causes Pituitary Stalk Interruption Syndrome and Combined Pituitary Hormone Deficiency

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A530-A530
Author(s):  
Hironori Bando ◽  
Michelle Brinkmeier ◽  
Peter Gergics ◽  
Qing Fang ◽  
Amanda Helen Mortensen ◽  
...  
Keyword(s):  
Pituitary Gland ◽  
Genetic Interaction ◽  
Pituitary Stalk ◽  
Hormone Deficiency ◽  
Pituitary Hormone ◽  
Beta Catenin ◽  
Loss Of Function ◽  
Rathke’S Pouch ◽  
Pituitary Development ◽  
Rathke's Pouch

Abstract The genetic basis for congenital hypopituitarism and related disorders is beginning to emerge, and over 30 causal genes have been identified. Mutations in some of these genes can also cause holoprosencephaly (HPE) or septo-optic dysplasia. SIX3 is a homeodomain protein expressed in the developing brain, pituitary gland, and eye. Heterozygous mutations in SIX3 cause variable HPE in humans and mice. We identified two children with neonatal GH and TSH deficiency and stalk interruption who were doubly heterozygous for rare, likely deleterious variants in SIX3 and POU1F1. Functional studies demonstrated that both variants are disruptive. We used Six3 and Pou1f1 loss of function mice to assess the genetic interaction between Six3 and Pou1f1. Six3 heterozygotes have variable pituitary gland dysmorphology, while Pou1f1 heterozygotes are normal. A significant portion of the Six3+/-; Pou1f1+/dw doubly heterozygous mice have a more pronounced pituitary phenotype than Six3+/-, supporting the possibility of digenic pituitary disease. To understand the role of SIX3 in pituitary and hypothalamic development, we used Prop1-cre and Nkx2.1-cre to delete Six3. Disruption of Six3 expression in Rathke’s pouch caused poor activation of Lhx3 expression and arrested anterior pituitary development. The Nkx2.1-cre, Six3flox/flox embryos had no evidence of infundibulum evagination and failed to induce FGF and BMP signaling, which normally drive expansion of Rathke’s pouch. By E11.5 cells in Rathke’s pouch underwent apoptosis. The Nkx2.1-cre, Six3flox/flox embryos failed to activate expression of Lhx2 and Tbx3 in the neural ectoderm. These embryos had elevated CCND1, MYCN, and Axin2 expression in the area of the presumptive infundibulum. This indicates that SIX3 is necessary to repress cell proliferation and Wnt/beta-catenin signals to promote formation of the pituitary stalk. Thus, Six3 has essential roles in both the neural and oral ectoderm for hypothalamic and pituitary development, respectively. Heterozygous loss of function variants in SIX3 could be a contributor to multiple pituitary hormone deficiencies in children, especially if there are associated craniofacial abnormalities or PSIS.

Accumulation of secretory granules in pituitary clonal cells derived from the epithelium of Rathke's pouch

1978 ◽  
Vol 186 (1) ◽  
Author(s):  
Masataka Shiino ◽  
Hiroshi Ishikawa ◽  
EdwardG. Rennels
Keyword(s):  
Secretory Granules ◽  
Rathke’S Pouch ◽  
Rathke's Pouch

Enhancement of the Canonical Wnt Pathway in Rathke's Pouch Results in Pituitary Tumours Reminiscent of Human Adamantinomatous Craniopharyngioma.

2010 ◽  
pp. OR38-3-OR38-3
Author(s):  
Carles Gaston-Massuet ◽  
Cynthia L Andoniadou ◽  
Massimo Signore ◽  
Sajutha Jayakody ◽  
Nicoletta Charolidi ◽  
...  
Keyword(s):  
Wnt Pathway ◽  
Pituitary Tumours ◽  
Rathke’S Pouch ◽  
Rathke's Pouch ◽  
Canonical Wnt Pathway ◽  
Adamantinomatous Craniopharyngioma ◽  
Canonical Wnt

Rathke's pouch morphogenesis in the chick embryo

1979 ◽  
Vol 207 (3) ◽  
pp. 351-366 ◽  
Author(s):  
Antone G. Jacobson ◽  
David M. Miyamoto ◽  
S.-H. Mai
Keyword(s):  
Chick Embryo ◽  
Rathke’S Pouch ◽  
Rathke's Pouch

Sellar enlargement with hyperprolactinemia and a Rathke's pouch cyst

JAMA ◽  
1978 ◽  
Vol 240 (5) ◽  
pp. 471-473 ◽  
Author(s):  
K. M. Trokoudes
Keyword(s):  
Rathke’S Pouch ◽  
Rathke's Pouch

scholarly journals Retinoic acid is required for specification of the ventral eye field and for Rathke's pouch in the avian embryo

2007 ◽  
Vol 51 (3) ◽  
pp. 191-200 ◽  
Author(s):  
Malcolm Maden ◽  
Aida Blentic ◽  
Susan Reijntjes ◽  
Sophie Seguin ◽  
Emily Gale ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Avian Embryo ◽  
Rathke’S Pouch ◽  
Rathke's Pouch ◽  
Eye Field
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