scholarly journals Conserved roles of Rax/rx3 genes in hypothalamus and pituitary development

Author(s):  
Flávio S. J. de Souza ◽  
Marysia Placzek

Rax (Rx) genes encode paired-type homeodomain-containing transcription factors pre-sent in virtually all metazoan groups. In vertebrates, studies in fish, amphibian, chick and mouse models have revealed that these genes play important roles in the development of structures lo-cated at the anterior portion of the central nervous system, in particular the eyes, the hypothala-mus and the pituitary gland. In addition, human patients with eye and brain defects carry muta-tions in the two human Rax paralogues, RAX and RAX2. Here, we review work done in the last years on Rax genes, focusing especially on the function that mouse Rax and its zebrafish homo-logue, rx3, play in hypothalamic and pituitary development. Work on both of these model organ-isms indicate that Rax genes are necessary for the patterning, growth and differentiation of the hypothalamus, in particular the dorso-anterior hypothalamus, where they effect their action by controlling expression of the secreted signalling protein, Sonic hedgehog (Shh). In addition, Rax/rx3 mutations disturb the development of the pituitary gland, mimicking phenotypes ob-served in human subjects carrying mutations in the RAX gene. Thus, along with their crucial role in eye morphogenesis, Rax genes play a conserved role in the development of the hypothalamus and adjacent structures in the vertebrate clade.

1963 ◽  
Vol 44 (3) ◽  
pp. 475-480 ◽  
Author(s):  
R. Grinberg

ABSTRACT Radiologically thyroidectomized female Swiss mice were injected intraperitoneally with 131I-labeled thyroxine (T4*), and were studied at time intervals of 30 minutes and 4, 28, 48 and 72 hours after injection, 10 mice for each time interval. The organs of the central nervous system and the pituitary glands were chromatographed, and likewise serum from the same animal. The chromatographic studies revealed a compound with the same mobility as 131I-labeled triiodothyronine in the organs of the CNS and in the pituitary gland, but this compound was not present in the serum. In most of the chromatographic studies, the peaks for I, T4 and T3 coincided with those for the standards. In several instances, however, such an exact coincidence was lacking. A tentative explanation for the presence of T3* in the pituitary gland following the injection of T4* is a deiodinating system in the pituitary gland or else the capacity of the pituitary gland to concentrate T3* formed in other organs. The presence of T3* is apparently a characteristic of most of the CNS (brain, midbrain, medulla and spinal cord); but in the case of the optic nerve, the compound is not present under the conditions of this study.


2020 ◽  
Vol 21 (10) ◽  
pp. 3672
Author(s):  
Pavel Ostasov ◽  
Jan Tuma ◽  
Pavel Pitule ◽  
Jiri Moravec ◽  
Zbynek Houdek ◽  
...  

Neural stem cells are fundamental to development of the central nervous system (CNS)—as well as its plasticity and regeneration—and represent a potential tool for neuro transplantation therapy and research. This study is focused on examination of the proliferation dynamic and fate of embryonic neural stem cells (eNSCs) under differentiating conditions. In this work, we analyzed eNSCs differentiating alone and in the presence of sonic hedgehog (SHH) or triiodothyronine (T3) which play an important role in the development of the CNS. We found that inhibition of the SHH pathway and activation of the T3 pathway increased cellular health and survival of differentiating eNSCs. In addition, T3 was able to increase the expression of the gene for the receptor smoothened (Smo), which is part of the SHH signaling cascade, while SHH increased the expression of the T3 receptor beta gene (Thrb). This might be the reason why the combination of SHH and T3 increased the expression of the thyroxine 5-deiodinase type III gene (Dio3), which inhibits T3 activity, which in turn affects cellular health and proliferation activity of eNSCs.


Neurosurgery ◽  
2004 ◽  
Vol 55 (1) ◽  
pp. 179-190 ◽  
Author(s):  
Alexandre Yasuda ◽  
Alvaro Campero ◽  
Carolina Martins ◽  
Albert L. Rhoton ◽  
Guilherme C. Ribas

Abstract OBJECTIVE: This study was conducted to clarify the boundaries, relationships, and components of the medial wall of the cavernous sinus (CS). METHODS: Forty CSs, examined under ×3 to ×40 magnification, were dissected from lateral to medial in a stepwise fashion to expose the medial wall. Four CSs were dissected starting from the midline to lateral. RESULTS: The medial wall of the CS has two parts: sellar and sphenoidal. The sellar part is a thin sheet that separates the pituitary fossa from the venous spaces in the CS. This part, although thin, provided a barrier without perforations or defects in all cadaveric specimens studied. The sphenoidal part is formed by the dura lining the carotid sulcus on the body of the sphenoid bone. In all of the cadaveric specimens, the medial wall seemed to be formed by a single layer of dura that could not be separated easily into two layers as could the lateral wall. The intracavernous carotid was determined to be in direct contact with the pituitary gland, being separated from it by only the thin sellar part of the medial wall in 52.5% of cases. In 39 of 40 CSs, the venous plexus and spaces in the CS extended into the narrow space between the intracavernous carotid and the dura lining the carotid sulcus, which forms the sphenoidal part of the medial wall. The lateral surface of the pituitary gland was divided axially into superior, middle and inferior thirds. The intracavernous carotid coursed lateral to some part of all the superior, middle, and inferior thirds in 27.5% of the CSs, along the inferior and middle thirds in 32.5%, along only the inferior third in 35%, and below the level of the gland and sellar floor in 5%. In 18 of the 40 CSs, the pituitary gland displaced the sellar part of the medial wall laterally and rested against the intracavernous carotid, and in 6 there was a tongue-like lateral protrusion of the gland that extended around a portion of the wall of the intracavernous carotid. No defects were observed in the sellar part of the medial wall, even in the presence of these protrusions. CONCLUSION: The CS has an identifiable medial wall that separates the CS from the sella and capsule of the pituitary gland. The medial wall has two segments, sellar and sphenoidal, and is formed by just one layer of dura that cannot be separated into two layers as can the lateral wall of the CS. In this study, the relationships between the medial wall and adjacent structures demonstrated a marked variability.


Development ◽  
1986 ◽  
Vol 95 (1) ◽  
pp. 1-14
Author(s):  
Gerald W. Eagleson ◽  
Bruce G. Jenks ◽  
A. P. van Overbeeke

A series of grafting experiments was conducted to determine pituitary origins prior to brain tube closure in Xenopus laevis. Extirpation experiments indicated that the ventral neural ridge (VNR) tissue of stage-18+ embryos was essential for pituitary development. Bolton–Hunter reagent was used to label stage-18+ VNR tissue with 125I, and this tissue was then returned to the donor and its subsequent ontogenesis followed. Labelled tissue was ultimately found in the ventral hypothalamus, the ventral retina, and the anterior pituitary. Using immunocytochemical techniques with antisera to adrenocorticotropin (ACTH), it was found that some of the VNR-derived cells were corticotropes. A region of the nucleus infundibularis which was radioactive labelled also gave ACTH-positive immunoreaction. This might indicate that some ACTH containing neurones of the hypothalamus are VNR in origin. We suggest that stage-18+ VNR is the site of attachment of brain and anterior pituitary ectoderm. Part of this adherence point is eventually incorporated into the anterior pituitary and will form corticotropes. It is concluded that the ventral retina, the preoptic region of the hypothalamus, some hypothalamic ACTH-immunoreactive cells, and the most anterior portion of the adenohypophysis are all ventral neural ridge in origin.


Author(s):  
Burdon Sanderson ◽  
F. Gotch

During the month of September, 1888, we availed ourselves of the facilities afforded by the Laboratory for the purpose of continuing the investigations began by us the year before, of the function of the electrical organ of the skate. In the record of the work done by us in 1887 at St. Andrews, published in the Journal of Physiology, vol. ix, p. 137, we indicated several new lines of investigation which we hoped to pursue if the opportunity offered. Two of these indications we have now been able to fulfil satisfactorily, namely, those relating to the electromotive force of the shock, and to the way in which the function of the electric organ is controlled and influenced by the central nervous system. In the first of these inquiries, we used apparatus which was brought from the Oxford Physiological Laboratory, and temporarily fitted up in the room at Plymouth, which is set apart for physiological researches, and which we found well adapted for this purpose. For the second, a large number of experiments and consequently a considerable number of fish were requisite. Forty skates of various species (Raia Batis, R. clavata, R. microcellata, and R. maculata) were supplied to us and used in our researches, of which the result will shortly be ready for publication.We desire to express in the strongest terms our appreciation of the advantages afforded by the Laboratory for physiological researches. We would also record our personal obligation to the Director for his uniform courtesy and untiring zeal in obtaining for us, in spite of considerable difficulties, the material required for our work.


Development ◽  
1997 ◽  
Vol 124 (14) ◽  
pp. 2709-2718 ◽  
Author(s):  
K. Shimamura ◽  
J.L. Rubenstein

The cellular and molecular mechanisms that regulate regional specification of the forebrain are largely unknown. We studied the expression of transcription factors in neural plate explants to identify tissues, and the molecules produced by these tissues, that regulate medial-lateral and local patterning of the prosencephalic neural plate. Molecular properties of the medial neural plate are regulated by the prechordal plate perhaps through the action of Sonic Hedgehog. By contrast, gene expression in the lateral neural plate is regulated by non-neural ectoderm and bone morphogenetic proteins. This suggests that the forebrain employs the same medial-lateral (ventral-dorsal) patterning mechanisms present in the rest of the central nervous system. We have also found that the anterior neural ridge regulates patterning of the anterior neural plate, perhaps through a mechanism that is distinct from those that regulate general medial-lateral patterning. The anterior neural ridge is essential for expression of BF1, a gene encoding a transcription factor required for regionalization and growth of the telencephalic and optic vesicles. In addition, the anterior neural ridge expresses Fgf8, and recombinant FGF8 protein is capable of inducing BF1, suggesting that FGF8 regulates the development of anterolateral neural plate derivatives. Furthermore, we provide evidence that the neural plate is subdivided into distinct anterior-posterior domains that have different responses to the inductive signals from the prechordal plate, Sonic Hedgehog, the anterior neural ridge and FGF8. In sum, these results suggest that regionalization of the forebrain primordia is established by several distinct patterning mechanisms: (1) anterior-posterior patterning creates transverse zones with differential competence within the neural plate, (2) patterning along the medial-lateral axis generates longitudinally aligned domains and (3) local inductive interactions, such as a signal(s) from the anterior neural ridge, further define the regional organization.


1937 ◽  
Vol 33 (9) ◽  
pp. 1142-1142
Author(s):  
B. Ivanov

In the picture of thyrotoxicosis, the foreground is the dysfunction of the thyroid gland; it should be borne in mind that the latter is under the influence of the central nervous system and hormonal centers (for example, the pituitary gland), changes in which affect the course and severity of the disease.


Author(s):  
Jinming Sun ◽  
Shaoli Wu ◽  
Philip A. Voglewede

The development of current prostheses and orthoses typically follows a trial and error approach where the devices are designed based on experience, tried on human subjects and then redesigned iteratively. This design approach is costly, risky and time consuming. A predictive human gait model is desired such that prostheses can be virtually tested so that their performance can be predicted qualitatively, the cost can be reduced, and the risks can be minimized. The development of such a model is explained in this paper. The developed model includes two parts: a plant model which represents the forward dynamics of human gait and a controller which represents the central nervous system (CNS). The development of the plant model is explained in a different paper. This paper focuses on the control algorithm development and able-bodied gait simulation. The controller proposed in this paper utilizes model predictive control (MPC). MPC uses an internal model to predict the output in advance, compare the predicted output to the reference, and optimize control input so that the error between them is minimal. The developed predictive human gait model was validated by simulating able-bodied human gait. The simulation results showed that the controller is able to simulate the kinematic output close to experimental data.


1968 ◽  
Vol 28 (2) ◽  
pp. 93-99 ◽  
Author(s):  
Richard M. Bergland ◽  
Bronson S. Ray ◽  
Richard M. Torack

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