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.

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.

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.

The homeodomain-containing gene Xdbx inhibits neuronal differentiation in the developing embryo

Development ◽  
2000 ◽  
Vol 127 (13) ◽  
pp. 2945-2954 ◽  
Author(s):  
A.A. Gershon ◽  
J. Rudnick ◽  
L. Kalam ◽  
K. Zimmerman
Keyword(s):  
Neuronal Differentiation ◽  
Normal Development ◽  
Early Embryo ◽  
Neural Plate ◽  
Neural Progenitors ◽  
Expression Domain ◽  
Basic Helix Loop Helix ◽  
Helix Loop Helix ◽  
Early Neurogenesis

The development of the vertebrate nervous system depends upon striking a balance between differentiating neurons and neural progenitors in the early embryo. Our findings suggest that the homeodomain-containing gene Xdbx regulates this balance by maintaining neural progenitor populations within specific regions of the neuroectoderm. In posterior regions of the Xenopus embryo, Xdbx is expressed in a bilaterally symmetric stripe that lies at the middle of the mediolateral axis of the neural plate. This stripe of Xdbx expression overlaps the expression domain of the proneural basic/helix-loop-helix-containing gene, Xash3, and is juxtaposed to the expression domains of Xenopus Neurogenin related 1 and N-tubulin, markers of early neurogenesis in the embryo. Xdbx overexpression inhibits neuronal differentiation in the embryo and when co-injected with Xash3, Xdbx inhibits the ability of Xash3 to induce ectopic neurogenesis. One role of Xdbx during normal development may therefore be to restrict spatially neuronal differentiation within the neural plate, possibly by altering the neuronal differentiation function of Xash3.

Developmental origin of the rat adenohypophysis prior to the formation of Rathke's pouch

Development ◽  
2001 ◽  
Vol 128 (6) ◽  
pp. 959-963
Author(s):  
T. Kouki ◽  
H. Imai ◽  
K. Aoto ◽  
K. Eto ◽  
S. Shioda ◽  
...  
Keyword(s):  
Neural Plate ◽  
Secretory Cells ◽  
Adjacent Area ◽  
Mammalian Embryo ◽  
Developmental Origin ◽  
Rathke’S Pouch ◽  
Rathke's Pouch ◽  
Early Mammalian Embryo ◽  
Mammalian Embryos ◽  
First Time

In amphibians, it has already been shown that the adenohypophysis originates from the anterior neural ridge. During the migration and morphogenesis of this organ, the anterior neural ridge transiently forms a Rathke's pouch-like structure by attaching itself to the rostral tip of the foregut, and finally gives rise to the adenohypophysis by detaching from the foregut and becoming connected to the infundibulum of the hypothalamus. In order to identify the origin of the adenohypophyseal cells in mammalian embryos prior to the formation of Rathke's pouch (RP), we labeled the rostral end of the neural plate and the adjacent area focally with DiI at the open neurula stage (9.5 dpc). After a 48-hours culture of the whole embryos, strongly labeled cells were detected in the RP only when DiI was applied to a small area situated just anterior to the rostral end of the neural plate. By explanting the labeled RP for a further 7 days, we confirmed immunohistochemically that the labeled cells developed into the secretory cells of the adenohypophysis. The developmental origin of the adenohypophysis is identified for the first time in the early mammalian embryo before the formation of RP.

scholarly journals A diverged homeobox gene is involved in the proliferation and lineage commitment of human hematopoietic progenitors and highly expressed in acute myelogenous leukemia

Blood ◽  
1992 ◽  
Vol 79 (11) ◽  
pp. 2841-2848 ◽  
Author(s):  
Y Deguchi ◽  
A Kirschenbaum ◽  
JH Kehrl
Keyword(s):  
Bone Marrow ◽  
Acute Myelogenous Leukemia ◽  
Homeobox Gene ◽  
Cell Types ◽  
Myelogenous Leukemia ◽  
Specific Cell ◽  
Hematopoietic Progenitors ◽  
Hematopoietic Progenitor ◽  
Cd34 Cells ◽  
Acute Myelogenous

HB24 is a diverged homeobox gene known to be expressed in hematopoietic progenitor cells. We show here that the inhibition of HB24 expression in CD34+ bone marrow cells via antisense (AS) oligonucleotides impaired the proliferation of these cells in response to interleukin-3 and granulocyte-macrophage colony-stimulating factor. The treatment of CD34+ cells with HB24 AS oligonucleotides also reduced the levels of c- fos, c-myc, c-myb, cyclin B, and p34cdc2 messenger RNAs compared with cells treated with control oligonucleotides. Conversely, the transient transfection of HB24 into a subpopulation of CD34 cells inhibited their differentiation into mature hematopoietic cell types. In addition, HB24 messenger RNA transcripts were elevated in bone marrow and peripheral blood mononuclear cells isolated from patients with acute myelogenous leukemia compared with normal controls. These data suggest that HB24 is an important transcription factor during hematopoietic progenitor proliferation and that differentiation to specific cell types requires its downregulation. Furthermore, dysregulated expression of HB24 impairs the normal differentiation of hematopoietic progenitors and may contribute to leukemogenesis.

scholarly journals Reduced expression of the LIM-homeobox gene Lhx3 impairs growth and differentiation of Rathke’s pouch and increases cell apoptosis during mouse pituitary development

2006 ◽  
Vol 123 (8) ◽  
pp. 605-613 ◽  
Author(s):  
Yangu Zhao ◽  
Donna Chelle Morales ◽  
Edit Hermesz ◽  
Woon-Kyu Lee ◽  
Samuel L. Pfaff ◽  
...  
Keyword(s):  
Cell Apoptosis ◽  
Homeobox Gene ◽  
Rathke’S Pouch ◽  
Pituitary Development ◽  
Rathke's Pouch ◽  
Mouse Pituitary

scholarly journals Patterning of the chick forebrain anlage by the prechordal plate

Development ◽  
1997 ◽  
Vol 124 (20) ◽  
pp. 4153-4162 ◽  
Author(s):  
E.M. Pera ◽  
M. Kessel
Keyword(s):  
Sonic Hedgehog ◽  
Neural Tube ◽  
Relative Concentration ◽  
Homeobox Gene ◽  
Primitive Streak ◽  
Lateral Side ◽  
Expression Domain ◽  
Prechordal Plate ◽  
Chick Forebrain

We analysed the role of the prechordal plate in forebrain development of chick embryos in vivo. After transplantation to uncommitted ectoderm a prechordal plate induces an ectopic, dorsoventrally patterned, forebrain-like vesicle. Grafting laterally under the anterior neural plate causes ventralization of the lateral side of the forebrain, as indicated by a second expression domain of the homeobox gene NKX2.1. Such a lateral ventralization cannot be induced by the secreted factor Sonic Hedgehog alone, as this is only able to distort the ventral forebrain medially. Removal of the prechordal plate does not reduce the rostrocaudal extent of the anterior neural tube, but leads to significant narrowing and cyclopia. Excision of the head process results in the caudal expansion of the NKX2.1 expression in the ventral part of the anterior neural tube, while PAX6 expression in the dorsal part remains unchanged. We suggest that there are three essential steps in early forebrain patterning, which culminate in the ventralization of the forebrain. First, anterior neuralization occurs at the primitive streak stage, when BMP-4-antagonizing factors emanate from the node and spread in a planar fashion to induce anterior neural ectoderm. Second, the anterior translocation of organizer-derived cells shifts the source of neuralizing factors anteriorly, where the relative concentration of BMP-4-antagonists is thus elevated, and the medial part of the prospective forebrain becomes competent to respond to ventralizing factors. Third, the forebrain anlage is ventralized by signals including Sonic Hedgehog, thereby creating a new identity, the prospective hypothalamus, which splits the eye anlage into two lateral domains.

scholarly journals A diverged homeobox gene is involved in the proliferation and lineage commitment of human hematopoietic progenitors and highly expressed in acute myelogenous leukemia

Blood ◽  
1992 ◽  
Vol 79 (11) ◽  
pp. 2841-2848 ◽  
Author(s):  
Y Deguchi ◽  
A Kirschenbaum ◽  
JH Kehrl
Keyword(s):  
Bone Marrow ◽  
Acute Myelogenous Leukemia ◽  
Homeobox Gene ◽  
Cell Types ◽  
Myelogenous Leukemia ◽  
Specific Cell ◽  
Hematopoietic Progenitors ◽  
Hematopoietic Progenitor ◽  
Cd34 Cells ◽  
Acute Myelogenous

Abstract HB24 is a diverged homeobox gene known to be expressed in hematopoietic progenitor cells. We show here that the inhibition of HB24 expression in CD34+ bone marrow cells via antisense (AS) oligonucleotides impaired the proliferation of these cells in response to interleukin-3 and granulocyte-macrophage colony-stimulating factor. The treatment of CD34+ cells with HB24 AS oligonucleotides also reduced the levels of c- fos, c-myc, c-myb, cyclin B, and p34cdc2 messenger RNAs compared with cells treated with control oligonucleotides. Conversely, the transient transfection of HB24 into a subpopulation of CD34 cells inhibited their differentiation into mature hematopoietic cell types. In addition, HB24 messenger RNA transcripts were elevated in bone marrow and peripheral blood mononuclear cells isolated from patients with acute myelogenous leukemia compared with normal controls. These data suggest that HB24 is an important transcription factor during hematopoietic progenitor proliferation and that differentiation to specific cell types requires its downregulation. Furthermore, dysregulated expression of HB24 impairs the normal differentiation of hematopoietic progenitors and may contribute to leukemogenesis.

scholarly journals Role of Xrx1 in Xenopus eye and anterior brain development

Development ◽  
1999 ◽  
Vol 126 (11) ◽  
pp. 2451-2460 ◽  
Author(s):  
M. Andreazzoli ◽  
G. Gestri ◽  
D. Angeloni ◽  
E. Menna ◽  
G. Barsacchi
Keyword(s):  
Brain Development ◽  
Transcriptional Activation ◽  
Homeobox Gene ◽  
Brain Regions ◽  
Neural Plate ◽  
Loss Of Function ◽  
Expression Domain ◽  
Severe Impairment ◽  
Development Analysis ◽  
Anterior Neural Plate

The anteriormost part of the neural plate is fated to give rise to the retina and anterior brain regions. In Xenopus, this territory is initially included within the expression domain of the bicoid-class homeobox gene Xotx2 but very soon, at the beginning of neurulation, it becomes devoid of Xotx2 transcripts in spatiotemporal concomitance with the transcriptional activation of the paired-like homeobox gene Xrx1. By use of gain- and loss-of-function approaches, we have studied the role played by Xrx1 in the anterior neural plate and its interactions with other anterior homeobox genes. We find that, at early neurula stage Xrx1 is able to repress Xotx2 expression, thus first defining the retina-diencephalon territory in the anterior neural plate. Overexpression studies indicate that Xrx1 possesses a proliferative activity that is coupled with the specification of anterior fate. Expression of a Xrx1 dominant repressor construct (Xrx1-EnR) results in a severe impairment of eye and anterior brain development. Analysis of several brain markers in early Xrx1-EnR-injected embryos reveals that anterior deletions are preceded by a reduction of anterior gene expression domains in the neural plate. Accordingly, expression of anterior markers is abolished or decreased in animal caps coinjected with the neural inducer chordin and the Xrx1-EnR construct. The lack of expansion of mid-hindbrain markers, and the increase of apoptosis in the anterior neural plate after Xrx1-EnR injection, indicate that anterior deletions result from an early loss of anterior neural plate territories rather than posteriorization of the neuroectoderm. Altogether, these data suggest that Xrx1 plays a role in assigning anterior and proliferative properties to the rostralmost part of the neural plate, thus being required for eye and anterior brain development.

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