Formation of Rathke's pouch requires dual induction from the diencephalon

Development ◽  
1998 ◽  
Vol 125 (23) ◽  
pp. 4835-4840 ◽  
Author(s):  
N. Takuma ◽  
H.Z. Sheng ◽  
Y. Furuta ◽  
J.M. Ward ◽  
K. Sharma ◽  
...  
Keyword(s):  
Regulatory Gene ◽  
Molecular Genetic ◽  
Homeobox Gene ◽  
Subsequent Development ◽  
Null Mutant ◽  
Rathke’S Pouch ◽  
Rathke's Pouch ◽  
Bmp4 Expression ◽  
Molecular Genetic Evidence

Targeted disruption of the homeobox gene T/ebp (Nkx2.1, Ttf1, Titf1) in mice results in ablation of the pituitary. Paradoxically, while T/ebp is expressed in the ventral diencephalon during forebrain formation, it is not expressed in Rathke's pouch or in the pituitary gland at any time of embryogenesis. Examination of pituitary development in the T/ebp homozygous null mutant embryos revealed that a pouch rudiment is initially formed but is eliminated by programmed cell death before formation of a definitive pouch. In the diencephalon of the mutant, Bmp4 expression is maintained, whereas Fgf8 expression is not detectable. These data and additional genetic and molecular observations suggest that Rathke's pouch develops in a two-step process that requires at least two sequential inductive signals from the diencephalon. First, BMP4 is required for induction and formation of the pouch rudiment, a role confirmed by analysis of Bmp4 homozygous null mutant embryos. Second, FGF8 is necessary for activation of the key regulatory gene Lhx3 and subsequent development of the pouch rudiment into a definitive pouch. This study provides firm molecular genetic evidence that morphogenesis of the pituitary primordium is induced in vivo by signals from the adjacent diencephalon.

Ontogenesis of hypothalamic immunoreactive ACTH cells in vivo and in vitro: Role of Rathke's pouch

1983 ◽  
Vol 97 (1) ◽  
pp. 81-88 ◽  
Author(s):  
Shigeo Daikoku ◽  
Mika Chikamori ◽  
Tohru Adachi ◽  
Yoshihito Okamura ◽  
Tohru Nishiyama ◽  
...  
Keyword(s):  
Rathke’S Pouch ◽  
Rathke's Pouch

Disruption of regulatory gene GAL80 in Saccharomyces cerevisiae: effects on carbon-controlled regulation of the galactose/melibiose pathway genes

1984 ◽  
Vol 4 (8) ◽  
pp. 1521-1527
Author(s):  
T E Torchia ◽  
R W Hamilton ◽  
C L Cano ◽  
J E Hopper
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Catabolite Repression ◽  
Carbon Catabolite Repression ◽  
Regulatory Gene ◽  
Negative Regulator ◽  
Null Mutation ◽  
Null Mutant ◽  
Wild Type

In Saccharomyces cerevisiae, the transcriptional expression of the galactose-melibiose catabolic pathway genes is under the control of at least three regulatory genes, GAL4, GAL80, and GAL3. We have isolated the GAL80 gene and have studied the effect of a null mutation on the carbon-controlled regulation of the MEL1 and GAL cluster genes. The null mutation was achieved in vivo by replacing the chromosomal wild-type GAL80 allele with an in vitro-created GAL80 deletion-disruption mutation. Enzyme activities and RNA levels for the GAL cluster and MEL1 genes were constitutively expressed in the null mutant strain grown on glycerol-lactate and were higher than in the isogenic wild-type yeast strain when compared after growth on galactose. Carbon catabolite repression of the GAL cluster and MEL1 genes, which occurs at the level of transcription, is retained in the null mutant. Deletion of the GAL80 gene in a gal4 cell does not restore GAL cluster and MEL1 gene expression. The data demonstrate that (i) the GAL80 protein is a purely negative regulator, (ii) the GAL80 protein does not mediate carbon catabolite repression, and (iii) the GAL4 protein is not simply an antagonizer of GAL80-mediated repression.

scholarly journals Disruption of regulatory gene GAL80 in Saccharomyces cerevisiae: effects on carbon-controlled regulation of the galactose/melibiose pathway genes.

1984 ◽  
Vol 4 (8) ◽  
pp. 1521-1527 ◽  
Author(s):  
T E Torchia ◽  
R W Hamilton ◽  
C L Cano ◽  
J E Hopper
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Catabolite Repression ◽  
Carbon Catabolite Repression ◽  
Regulatory Gene ◽  
Negative Regulator ◽  
Null Mutation ◽  
Null Mutant ◽  
Wild Type

In Saccharomyces cerevisiae, the transcriptional expression of the galactose-melibiose catabolic pathway genes is under the control of at least three regulatory genes, GAL4, GAL80, and GAL3. We have isolated the GAL80 gene and have studied the effect of a null mutation on the carbon-controlled regulation of the MEL1 and GAL cluster genes. The null mutation was achieved in vivo by replacing the chromosomal wild-type GAL80 allele with an in vitro-created GAL80 deletion-disruption mutation. Enzyme activities and RNA levels for the GAL cluster and MEL1 genes were constitutively expressed in the null mutant strain grown on glycerol-lactate and were higher than in the isogenic wild-type yeast strain when compared after growth on galactose. Carbon catabolite repression of the GAL cluster and MEL1 genes, which occurs at the level of transcription, is retained in the null mutant. Deletion of the GAL80 gene in a gal4 cell does not restore GAL cluster and MEL1 gene expression. The data demonstrate that (i) the GAL80 protein is a purely negative regulator, (ii) the GAL80 protein does not mediate carbon catabolite repression, and (iii) the GAL4 protein is not simply an antagonizer of GAL80-mediated repression.

Pitx2is required at multiple stages of pituitary organogenesis: pituitary primordium formation and cell specification

Development ◽  
2002 ◽  
Vol 129 (2) ◽  
pp. 329-337 ◽  
Author(s):  
Hoonkyo Suh ◽  
Philip J. Gage ◽  
Jacques Drouin ◽  
Sally A. Camper
Keyword(s):  
Transcription Factors ◽  
Homeobox Gene ◽  
Threshold Level ◽  
Cell Types ◽  
Allelic Series ◽  
Rieger Syndrome ◽  
Rathke’S Pouch ◽  
Pituitary Development ◽  
Rathke's Pouch ◽  
Multiple Stages

Analysis of an allelic series in mice revealed that the Pitx2 homeobox gene is required at multiple stages of pituitary development. It is necessary for initiating expansion of Rathke’s pouch and maintaining expression of the fetal-specific transcription factors Hesx1 and Prop1. At later stages Pitx2 is necessary for specification and expansion of the gonadotropes and Pit1 lineage within the ventral and caudomedial anterior pituitary. Mechanistically, this is due to the dependence of several critical lineage-specific transcription factors, Pit1, Gata2, Egr1 and Sf1, on a threshold level of PITX2. The related Pitx1 gene has a role in hormone gene transcription, and it is important late in ontogeny for the final expansion of the differentiated cell types. Pitx1 and Pitx2 have overlapping functions in the expansion of Rathke’s pouch, revealing the sensitivity of pituitary organogenesis to the dosage of the PITX family. The model developed for PITX gene function in pituitary development provides a better understanding of the etiology of Rieger syndrome and may extend to other PITX-sensitive developmental processes.

Abstract 1614: Inducible Nitric Oxide Synthase Upregulates Heme Oxygenase-1 (HO-1) in Myocardium by Enhancing Nrf2 Phosphorylation and Binding to the HO-1 Promoter

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Qianhong Li ◽  
Qinghui Ou ◽  
Wei Tan ◽  
Wen-Jian Wu ◽  
Xiaoping Zhu ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Gene Transfer ◽  
Molecular Genetic ◽  
Gene Promoter ◽  
Heme Oxygenase 1 ◽  
Nuclear Fraction ◽  
List Type ◽  
Inos Gene ◽  
Molecular Genetic Evidence

Previous studies have shown that iNOS gene transfer leads to elevated expression of HO-1, which in turn protects against ischemic injury. However, the mechanism of this effect is unknown. Recently, Nrf2 has emerged as a key transcription factor in response to stress. Thus, we hypothesized that the upregulation of HO-1 by iNOS gene therapy involves an Nrf2-mediated pathway. Mice received injections in anterior LV wall of Av3/LacZ or Av3/iNOS; 3 days later, they were subjected to a 30-min coronary occlusion and 4 h of reperfusion. At 24 h after iNOS gene transfer (confirmed by iNOS immunoblotting), phosphorylated Nrf2 increased significantly in the myocardial nuclear fraction (+ 220% vs. LacZ group, n=6, P<0.05; Fig ); chromatin Nrf2-immunoprecipitation (Nrf2-ChIP) analysis in vivo showed that Nrf2 was specifically recruited to the HO-1 gene promoter (+ 4.7-fold vs. LacZ group, n=4, P<0.05; Fig ). At 3 days after iNOS gene transfer, myocardial HO-1 protein expression increased markedly (+ 2.6-fold vs. LacZ group, n=6, P<0.05; Fig ), but HO-2 did not change (n=3). The infarct-sparing effects of iNOS gene therapy were completely abrogated by disruption of Nrf2 (Nrf2−/−) (62.8±2.1% in Nrf2−/−+Av3/iNOS group, n=5, vs. 15.3±4.3% in WT+Av3/iNOS group, n=7; Fig ). We conclude that iNOS upregulates HO-1 by enhancing Nrf2 phosphorylation and binding to the HO-1 promoter; and targeted disruption of the Nrf2 gene completely abrogates cardioprotection after iNOS gene transfer. These results provide unequivocal molecular genetic evidence for a necessary role of Nrf2 in the protection afforded by iNOS. Thus, activation of Nrf2 is a key molecular event that links iNOS to HO-1.

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.

Rpx: a novel anterior-restricted homeobox gene progressively activated in the prechordal plate, anterior neural plate and Rathke's pouch of the mouse embryo

Development ◽  
1996 ◽  
Vol 122 (1) ◽  
pp. 41-52 ◽  
Author(s):  
E. Hermesz ◽  
S. Mackem ◽  
K.A. Mahon
Keyword(s):  
Homeobox Gene ◽  
Cell Types ◽  
Early Embryo ◽  
Neural Plate ◽  
Specific Cell ◽  
Expression Domain ◽  
Rathke’S Pouch ◽  
Rathke's Pouch ◽  
Prechordal Plate ◽  
Early Expression

We have isolated a new murine homeobox gene, Rpx (for Rathke's pouch homeobox), that is dynamically expressed in the prospective cephalic region of the embryo during gastrulation. Early expression is seen in the anterior midline endoderm and prechordal plate precursor. Expression is subsequently activated in the overlying ectoderm of the cephalic neural plate, suggesting that inductive contact with Rpx-expressing mesendoderm is required for this expression. Subsequently, Rpx expression is extinguished in the mesendoderm while remaining in the prospective prosencephalic region of the neural plate ectoderm. Ultimately, transcripts become restricted to Rathke's pouch, the primordium of the pituitary, which is known to be derived from the most anterior ectoderm of the early embryo. Down regulation of Rpx in the pouch coincides with the differentiation of pituitary-specific cell types. Rpx is the earliest known marker for the pituitary primordium, suggestive of a role in the early determination or differentiation of the pituitary. Since Rpx is expressed so dynamically and so early in the anterior region of the embryo, and since its early expression domain is much more extensive than the region fated to form the pituitary, it is likely that Rpx is involved in the initial determination of the anterior (prechordal) region of the embryo.

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