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Origin of the ultimobranchial body cyst: T/ebp/Nkx2.1 expression is required for development and fusion of the ultimobranchial body to the thyroid.

The ultimobranchial body (UBB) is an outpocketing of the fourth pharyngeal pouch that fuses with the thyroid diverticulum, giving rise to calcitonin-producing C-cells. In this study, we demonstrate that the UBB is composed of two types of cells: one expressing T/ebp/Nkx2.1 and the other expressing p63. The former cell type, accounting for a majority of the UBB, requires T/ebp/Nkx2.1 for their survival. In contrast, the p63-positive cells, even in the absence of T/ebp/Nkx2.1 expression, can proliferate and give rise to a vesicular structure that is lined by a monolayer of p63-negative cells, surrounded by a cluster and/or single layer of p63-positive cells, displaying the basal/stem cell phenotype. T/ebp/Nkx2.1 haploinsufficiency causes abnormal fusion of the UBB with the thyroid diverticulum, which stays as a cluster of C-cells around the vesicular structure, similar to the one observed in mice null for T/ebp/Nkx2.1 expression. These results demonstrate that T/ebp/Nkx2.1 plays a role in the survival of UBB cells, their dissemination into the thyroid diverticulum, and the formation of UBB-derived vesicular structure.

Animals↗

Structure of rat ultimobranchial bodies after birth.

The evolution of ultimobranchial bodies in Holtzman rats during the first 64 weeks after birth was studied by reconstructing three-dimensional models from serial sections stained by the periodic acid-Schiff technique.Radio-autography with 125I was made to see if ultimobranchial cells and/or follicular cells lining the lumen of mixed follicles were able to iodinate proteins. The term ultimobranchial body designates herein an embryonic vesicular structure (derived from the third pharyngeal pouch) whose wall is made of stratified squamous epithelium. During the first week after birth, the vesicular ultimobranchial body elongates rapidly and becomes a canal or a duct. During the second week, cell desquamation brings about local dilatations in the lumen of these ducts; with further enlargement ultimobranchial follicles will appear. In one-day-old rats, mixed follicles are present. Only the follicular component of mixed follicles iodinates proteins as is shown by radioautography. The reconstructed models enlarge rapidly up to the 56th day after birth at which time their weight has increased nineteenfold. These same models show that the three morphological components of ultimobranchial parenchyma, namely ducts, follicles and mixed follicles, are in continuity within the thyroid parenchyma. The formation of new thyroid follicles after birth and the possiblility that the ultimobranchial parenchyma may function as an endocrine gland of holocrine type are discussed.

Age Factors↗

A morphological and immunohistochemical study of the ultimobranchial body in the Japanese lizard and the snake.

A morphological and immunohistochemical study of the ultimobranchial body of reptiles Japanese lizard and snake was carried out. The ultimobranchial body of the Japanese lizard was located adjacent to the left arch of the aorta between the trachea and esophagus. It was found as a cluster or group of cells with no capsule. Grimelius' silver impregnation and lead-hematoxylin staining produced positive reactions in some of the clustered cells and follicular cells. The same reaction pattern was observed with anti-calcitonin using the PAP method. The PAP reactions were positive to antiserum against pig calcitonin, but negative to antiserum against synthesized human calcitonin. Furthermore, the PAP reactions were negative to antiserum against tyrosine hydroxylase. The immunofluorescent study of the snake ultimobranchial body revealed that most of the clustered cells and some of the follicular cells were calcitonin-immunoreactive but none was tyrosine hydroxylase-immunoreactive. Certain histological similarities exist between the Japanese lizard ultimobranchial body and snake ultimobranchial body, but the distribution of calcitonin-positive cells were slightly different. In the Japanese lizard, the positive cells were scattered between the foliicles and the number was small. However, most of the cells which formed the cluster in the ultimobranchial body of snake were positive. The findings suggest that the configuration of amino acid in the Japanese lizard calcitonin and snake calcitonin are similar to that of pig calcitonin, and the reptile and the birds is a boundary of the tyrosine hydroxylase existence.

Animals↗

Parathyroids and ultimobranchial bodies in monotremes.

Only scant information is available in the scientific literature on the parathyroids and ultimobranchial bodies in the primitive mammals, the echidna (Tachyglossus aculeatus) and platypus (Ornithorhynchus anatinus). The major aim of this paper is to describe the morphology of the monotreme parathyroid gland and to compare it with parathyroids in mammals and reptiles. The gross anatomy and light microscopic structure of the ultimobranchial body, thymus, and thyroid are also given. Animals were dissected and routine light and electron microscopic techniques used to examine the microscopic morphology. The locations of parathyroid hormone, calcitonin and calcitonin gene-related peptide in tissue sections were identified by immunostaining. Monotremes have one pair of parathyroid glands located in the thorax and they are often associated with thymic tissue but never with the thyroid which is also present in the mediastinum. Ultimobranchial bodies are ventrolateral to the commencement of the trachea. Thymic lobules with Hassall's corpuscles are scattered in the fibrofatty tissue of the mediastinum and the ventral surface of the pericardium. Histologically, principal cells, water-clear cells, and non-secretory cells were identified in the parathyroid glands. Principal cells showed polarity and had microlamellar projections that formed intercellular canaliculi. Non-secretory cells had features similar to those of thymic epithelial reticular cells. Immunostaining of parathyroid hormone showed a diffuse distribution in parathyroid principal cells and none in ultimobranchial bodies. Identification of the ultimobranchial bodies was confirmed by immunostaining. The monotreme parathyroid gland, ultimobranchial bodies and thyroid show reptilian as well as mammalian features.

Animals↗

Morphogenesis of the ultimobranchial body and its colonizing cells in the chick embryo.

The development of the ultimobranchial body and its colonizing cells was studied in chick embryos in Hamburger-Hamilton's stages 21 to 46. The most significant observations included the following: 1.-The ultimobranchial body is a separate morphological entity with particular characteristics distinguishing it from the fourth pharyngeal pouch in all developmental stages. 2.-The fifth pharyngeobranchial ducts disappear in Hamburger-Hamilton's stage 27. 3.-From Hamburger-Hamilton's stage 27 on, the left ultimobranchial body is in contact with the caudal end of the left parathyroid IV primordium. 4.-The group made up of the ultimobranchial body and its colonizing cells at no time fuses with the thyroid gland.

Animals↗

[Immunohistochemical and morphometric studies on the development of the thyroid, parathyroid and ultimobranchial body in Xenopus laevis Daudin].

The development of the thyroid, parathyroid and ultimobranchial body was examined by immunohistochemistry and morphometric analysis in the larvae of Xenopus laevis Daudin from the time immediately after hatch to the end of metamorphosis. The thyroid appeared at stage 43 and began to secrete thyroglobulin from stage 47/48. Both the volume of the thyroid and the height of the follicular epithelium reached the peak at stage 61 and decreased thereafter towards the end of metamorphosis at stage 66. The parathyroid first appeared at stage 43 as the thickening of the wall of the third and fourth visceral pouch. The volume of the parathyroid gradually increased with the progress of development until the end of metamorphosis. The ultimobranchial body appeared at stage 45 as a recess of the epithelium lining the floor of the pharynx. It became follicular in the structure at stage 53. Its volume reached the peak at stage 61 and decreased thereafter towards the end of metamorphosis. Calcitonin-immunoreactive cells first appeared in the ultimobranchial body at stage 47/48, showed the most intense reaction at stage 59, and rapidly decreased in number thereafter towards the end of metamorphosis.

Animals↗

Origin of the ultimobranchial body and its colonizing cells in human embryos.

The early development of the ultimobranchial body and its colonizing cells was studied in human embryos (O'Rahilly's stages 14 and 15). In our studies we have obtained evidence that permits us to propose a new hypothesis on the origin of both the ultimobranchial body and its colonizing cells. Based on our interpretation of the morphogenetic features in human development, we think that the ultimobranchial body derives from the fifth endodermal pharyngeal pouch, which is colonized, from O'Rahilly's stage 14 on, by cellular material of ectodermal placodial nature that originates in the most caudal portion of the epicardiac branchial placode.

Animals↗

A morphological study of the ultimobranchial body in the grass parakeet.

As parafollicular cells can be stained by Grimelius' silver impregnation and by lead-hematoxylin, the ultimobranchial body cells, homologous to them, seem to also react positively to these methods. In the present study of the ultimobranchial body of the grass parakeet, mirror-image sections were stained by both methods and compared. While about 50% of the cells reacted positively to both Grimelius' silver impregnation and lead-hematoxylin staining, only about 20% were positive to the former and about 30% were positive to the latter only. This result indicating heterogeneity among the cells of the ultimobranchial body of the grass parakeet suggests a possible occurrence of cells secreting substances other than calcitonin.

Animals↗

[Seasonal variations of the ultimobranchial body of the turtle (Pseudemys scripta)].

Ultrastructural seasonal cyclic aspects of ultimobranchial body (C.U.B.) in fresh turtles (Pseudemys scripta) are studied. The C.U.B. consists of follicles and cords. The cord cells are characterized by many secretory granules measuring approximately 180 nm with variable feature and electron density. These granules are localized in the cytoplasm close to basal laminae. The follicular cells, on the contrary, present few and large secretory granules, glycogen particles, bundle of filaments and a scarcely developing Golgi apparatus and granular endoplasmic reticulum. The apical and follicular cytoplasmatic membrane is provided with small number of cilia and short microvilli. Seasonal cellular variations are described clearly in the winter (february-march) specimens of ultimobranchial body, these are characterized by more cord aspects and few follicles. The only cord cells present significant ultrastructural changes, represented by more glycogen particles, middle and wide lipid droplets and poor presecretory granules in Golgi zone. These morphological elements orient to a parallelism with the C cells of hibernant animals (Azzali 1967, Frink and Coll.) and the chief cells of parathyroid gland of the self turtle species as by our previous study.

Animals↗

Position of ultimobranchial body cysts in the human fetal thyroid gland.

In a series of 21 human fetal thyroid glands examined histologically in serial sections, seven ultimobranchial body cysts were found. The position of these cysts correlated well with the distribution of calcitonin-containing cells found by previous investigators in the adult thyroid gland. Ultimobranchial body cysts found external to the thyroid lobes may offer a developmental explanation for the paucity of calcitonin found in some adult thyroid glands. The close developmental relationship between the parathyroid gland and the ultimobranchial body could explain the presence of calcitonin found in these glands in some adults.

Animals↗

Observations on the fine structure, enzyme histochemistry, and innervation of parathyroid gland and ultimobranchial body of Chthonerpeton indistinctum (Gymnophiona, Amphibia).

Fine structural and enzyme histochemical observations on ultimobranchial body and parathyroid gland of the caecilian Chthonerpeton are presented. The cell clusters and follicles of the ultimobranchial body consist mainly of granulated cells which are termed C-cells and obviously belong to the APUD cell series. In the larger follicles additional possibly exhausted degranulated cells and replacement cells occur. A rich supply of nerve fibres has been found in this gland. Frequently nerve terminals were observed to come into synaptic contact with the C-cells. Two categories of nerve fibres occur: a) fibres containing large polymorphic electron dense granules (probably purinergic fibres), b) fibres containing small electron transparent vesicles and a few electron dense granules (probably cholinergic fibres). The parathyroid gland consists of elongated cells (one cell type) poor in organelles and often containing fields of glycogen and lipid droplets. The cells are further characterized by fair amounts of lysosomal enzymes; they are interconnected by maculae adhaerentes and occludentes. No nerves and blood vessels have been found in the parathyroid gland of Chthonerpeton.

Acid Phosphatase↗

[The effect of weightlessness on amphibians. The ultimobranchial body].

C-cells of Pleurodeles waltilii ultimobranchial bodies (ULT) were studied after a series of two-week spaceflight on the biosatellites. It was shown that under conditions of weightlessness the hypertrophy of ULT and calcitonin secretion activation occurred. Calcitonin accumulated into the ULT which resulted in metaplasia of the surrounding tissues, organ calcification and C-cells death. After landing, the regenerative processes which were not manifest in weightlessness occurred. They were similar to those of embryonic development of the organ.

Adaptation, Physiological↗

Ultimobranchial body and parathyroid gland of the frog, Rana tigrina in response to calcitonin administration.

The effects of salmon calcitonin (0.25 MRC mU/g body wt) on the serum calcium and phosphate levels as well as on the activity of ultimobranchial body and parathyroid glands was investigated in the frog, Rana tigrina for 15 days. The hormone evokes hypocalcemia (on day 1 and day 3) which is followed by a significant hypercalcemia on day 10. Thereafter, the level of calcium decreases again on day 15. Calcitonin induces hypophosphatemia (on day 3 and day 5). Thereafter, hyperphosphatemia is recorded on day 10. By day 15 normal serum phosphate value is achieved. After treatment with calcitonin, the ultimobranchial body becomes inactive and the parathyroid glands get activated.

Animals↗

Fine structure of the ultimobranchial body of the pheasant (Phasianus colchicus L.).

The pheasant's ultimobranchial body is characterized by the presence, in the connective tissue stroma, of epithelial cells between which two types of granulated cells comprising the main part of the glandular portion of the body are formed. Type I is characterized chiefly by the presence of nonrounded electron-dense secretory granules measuring 65-240 nm in the cytoplasm and by a very well-developed Golgi apparatus. The cytoplasm of type II cells also contains dark secretory granules, but somewhat smaller (50-150 nm). This type is very frequently in close contact with specific and often branching tubular structures from whose cells microvilli project into the lumen. The dark cytoplasm of the cells lining these structures contains a relatively large number of mitochondria and dense bodies, but no secretory granules.

Animals↗

Ultimobranchial body cysts in the human foetal thyroid: pathological implications.

In a histological study of 28 human foetal thyroids, ultimobranchial body cysts were found in seven foetuses. Large oval cells were seen adjacent to or within the cysts. There is a morphological resemblance between the cells associated with the ultimobranchial cysts and those of medullary carcinoma of the thyroid gland. This similarity, in humans, substantiates the hypothesis that medullary carcinoma arises from the parafollicular cells, which themselves are known to differentiate from ultimobranchial body tissue.

Cysts↗