SOME ASPECTS OF EARLY DEVELOPMENT OF THE THYMUS: EMBRYOLOGICAL BASIS FOR ECTOPIC THYMUS AND THYMOPHARYNGEAL DUCT CYST.  Algunas observaciones acerca del temprano desarrollo del timo: bases embriológicas del timo ectópico y del quiste del conducto timofar

Introducción. El objetivo principal de nuestro trabajo es el estudio histológico del desarrollo del timo humano entre la 5ª y la 8ª semana de gestación. Describimos varios términos embriológicos poco usados como: timo secundus, descensus thymi (la base embriológica para situar el timo en la garganta), ductus timicus (la base embriológica para el defecto innato llamado conducto timofaríngeo con posibilidad de formar un quiste). Material y método. Nuestras observaciones se basan en la investigación de 18 embriones humanos entre la 6ª y la 8ª semana de gestación. Resultados. La base del timo es común con la base de las glándulas paratiroideas. Es comparable con las bolsas faríngeas (saccus pharyngeus) en los embriones largos de 8 a 9 mm. La proliferación endodermal del epitelio en el tercer foco faríngeo (focus faringeus 3) es muy visible. La parte craneal y la parte dorsal son la base de origen de las glándulas paratiroideas inferiores. La parte caudal y la parte ventral son la base para el timo. Hemos observado también la notable proliferación del epitelio en la segunda bolsa faríngea, llamado por algunos autores Timo secundus. En nuestra opinión, en el ser humano no se forma un timo funcional en este lugar y la proliferación del epitelio en la mayoría de los casos, se detiene pronto. Conclusión. En este trabajo ofrecemos una vista general sobre la importancia clínica del desarrollo del timo y la descripción de los defectos innatos más frecuentes del mismo. Introduction. The aim of our morphological study is to describe the development of human thymus from 5th up to 8th week after fertilization in the context of its phylogenesis. We explicate some of the “forgotten” embryological terms with respect to their functions in thymic development, such as “thymus secundus”, “descensus thymi” (an embryological basis for cervical thymus) and “ductus thymicus” (an embryologic basis for a congenital anomaly called thymopharyngeal duct with possible thymic cyst). Material and methods. Our findings are based on the study of 18 human embryos from 6th to 8th week of development. Results. The first primordia of the thymus and parathyroid glands within the endoderm of pharyngeal pouches can be seen in 8 to 9 mm crown-to-rump-length stages. The most evident epithelial proliferation is visible in the paired third pharyngeal pouch (saccus pharyngeus tertius): the cranial dorsal part of pharyngeal pouch initiates the inferior parathyroid gland and the caudal ventral part of the pouch gives rise to the epithelial thymus. We found an obvious endodermal epithelial proliferation also in the second pharyngeal pouch. Some authors depict this proliferation as “thymus secundus”, but the proliferation of endoderm close down and the functional second thymus does not develop in human embryos. Conclusion. In our work we also review the clinical significance of early thymus development, as well as the most common developmental anomalies of thymus.

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EXTIRPATION OF THE THYMUS IN THE GUINEA PIG

Journal of Experimental Medicine ◽

10.1084/jem.25.1.129 ◽

1917 ◽

Vol 25 (1) ◽

pp. 129-152 ◽

Cited By ~ 15

Author(s):

Edwards A. Park

Keyword(s):

Guinea Pig ◽

Serial Section ◽

Guinea Pigs ◽

Close Association ◽

Main Lobe ◽

Technical Error ◽

Serial Sections ◽

Pharyngeal Pouch ◽

The Third ◽

Third Pharyngeal Pouch

1. Accessory lobes of thymus, derived from the third pharyngeal pouch, occurring in close association with the parathyroids from the third pouch, were found in serial section of the cervical tissues of eleven out of fourteen guinea pigs, and probably would have been found in all fourteen but for a technical error. 2. It is probable, therefore, that accessory lobes of thymus having this situation and origin are usually, if not always, present in the guinea pig. 3. Additional accessory lobes of thymus belonging to, but at some distance from the main lobe were also present in several of the animals. 4. The discovery of these accessory lobes makes it certain that the guinea pig is unsuitable material for complete thymectomy, and probably complete extirpation of the thymus in this animal is rarely, if ever accomplished. 5. The extirpation experiments of previous investigators in the guinea pig must now be regarded as partial extirpations, and their results interpreted in that light. 6. Extirpation of the thymus in the guinea pig produced no changes in the writer's experiments. 7. The study of the serial sections of the cervical tissues of the guinea pig indicates that Ruben's statements regarding the parathyroid derived from the fourth pharyngeal pouch in the guinea pig are correct,—that it is much smaller than parathyroid III, may be rudimentary, and is sometimes absent at least on one side. 8. No accessory lobe of thymus was found accompanying the parathyroid from the fourth pouch, a finding also bearing out Ruben's statement that no thymus anlarge springs from the fourth pouch in the guinea pig.

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Pax1 is expressed during development of the thymus epithelium and is required for normal T-cell maturation

Development ◽

10.1242/dev.122.1.23 ◽

1996 ◽

Vol 122 (1) ◽

pp. 23-30 ◽

Cited By ~ 27

Author(s):

J. Wallin ◽

H. Eibel ◽

A. Neubuser ◽

J. Wilting ◽

H. Koseki ◽

...

Keyword(s):

T Cell ◽

Regulatory Protein ◽

Cell Maturation ◽

Thymic Epithelial Cells ◽

Total Size ◽

Thymic Development ◽

Transcriptional Regulatory ◽

Thymus Cells ◽

T Cell Maturation ◽

Third Pharyngeal Pouch

Pax1 is a transcriptional regulatory protein expressed during mouse embryogenesis and has been shown to have an important function in vertebral column development. Expression of Pax1 mRNA in the embryonic thymus has been reported previously. Here we show that Pax1 protein expression in thymic epithelial cells can be detected throughout thymic development and in the adult. Expression starts in the early endodermal epithelium lining the foregut region and includes the epithelium of the third pharyngeal pouch, a structure giving rise to part of the thymus epithelium. In early stages of thymus development a large proportion of thymus cells expresses Pax1. With increasing age, the proportion of Pax1-expressing cells is reduced and in the adult mouse only a small fraction of cortical thymic stromal cells retains strong Pax1 expression. Expression of Pax1 in thymus epithelium is necessary for establishing the thymus microenvironment required for normal T cell maturation. Mutations in the Pax-1 gene in undulated mice affect not only the total size of the thymus but also the maturation of thymocytes. The number of thymocytes is reduced about 2- to 5-fold, affecting mainly the CD4+8+ immature and CD4+ mature thymocyte subsets. The expression levels of major thymocyte surface markers remains unchanged with the exception of Thy-1 which was found to be expressed at 3- to 4-fold higher levels.

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Third pharyngeal pouch sinuses: Report of a bilateral case with a review of the embryology and literature

Clinical Anatomy ◽

10.1002/ca.980040406 ◽

1991 ◽

Vol 4 (4) ◽

pp. 285-297 ◽

Cited By ~ 2

Author(s):

Wesley W. Parke ◽

Harry E. Settles

Keyword(s):

Pharyngeal Pouch ◽

Bilateral Case ◽

Third Pharyngeal Pouch

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Undescended retropharyngeal parathyroid adenoma with adjacent thymic tissue in a 13-year-old boy with primary hyperparathyroidism

Oxford Medical Case Reports ◽

10.1093/omcr/omz129 ◽

2019 ◽

Vol 2019 (12) ◽

pp. 519-523 ◽

Cited By ~ 1

Author(s):

Anthony M Kordahi ◽

Ron S Newfield ◽

Stephen W Bickler ◽

Jun Q Mo ◽

Paritosh C Khanna ◽

...

Keyword(s):

Primary Hyperparathyroidism ◽

Ct Scan ◽

Parathyroid Adenoma ◽

Pharyngeal Pouch ◽

Rare Presentation ◽

Thymic Tissue ◽

The Third ◽

Parathyroid Adenomas ◽

Preoperative Ct ◽

Third Pharyngeal Pouch

ABSTRACT We describe a rare presentation of a symptomatic parathyroid adenoma located in an ectopic retropharyngeal position in a 13-year-old boy. Preoperative CT scan and MRI demonstrated the ectopic location of the parathyroid adenoma. The patient underwent successful parathyroidectomy with cure of his hyperparathyroidism. On pathologic exam, the specimen was made up of a parathyroid adenoma and adjacent thymic tissue, indicating that it was likely an undescended lower parathyroid gland arising from the third pharyngeal pouch. Ectopic retropharyngeal parathyroid adenomas are very rare and to our knowledge, none have been previously described in adolescents.

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Localised inhibition of FGF signalling in the third pharyngeal pouch is required for normal thymus and parathyroid organogenesis

Development ◽

10.1242/dev.079400 ◽

2012 ◽

Vol 139 (18) ◽

pp. 3456-3466 ◽

Cited By ~ 20

Author(s):

J. R. Gardiner ◽

A. L. Jackson ◽

J. Gordon ◽

H. Lickert ◽

N. R. Manley ◽

...

Keyword(s):

Pharyngeal Pouch ◽

The Third ◽

Fgf Signalling ◽

Third Pharyngeal Pouch

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Gene expression profile of the third pharyngeal pouch reveals role of mesenchymal MafB in embryonic thymus development

Blood ◽

10.1182/blood-2008-06-164921 ◽

2009 ◽

Vol 113 (13) ◽

pp. 2976-2987 ◽

Cited By ~ 10

Author(s):

Dil Afroz Sultana ◽

Shuhei Tomita ◽

Michito Hamada ◽

Yasuyuki Iwanaga ◽

Yuki Kitahama ◽

...

Keyword(s):

Gene Expression ◽

Mesenchymal Cells ◽

Pharyngeal Pouch ◽

Cdna Subtraction ◽

Cell Repertoire ◽

The Third ◽

Polymerase Chain ◽

Deficient Mice ◽

Third Pharyngeal Pouch

Abstract The thymus provides a microenvironment that induces the differentiation of T-progenitor cells into functional T cells and that establishes a diverse yet self-tolerant T-cell repertoire. However, the mechanisms that lead to the development of the thymus are incompletely understood. We report herein the results of screening for genes that are expressed in the third pharyngeal pouch, which contains thymic primordium. Polymerase chain reaction (PCR)–based cDNA subtraction screening for genes expressed in microdissected tissues of the third pharyngeal pouch rather than the second pharyngeal arch yielded one transcription factor, MafB, which was predominantly expressed in CD45−IA−PDGFRα+ mesenchymal cells and was detectable even in the third pharyngeal pouch of FoxN1-deficient nude mice. Interestingly, the number of CD45+ cells that initially accumulated in the embryonic thymus was significantly decreased in MafB-deficient mice. Alterations of gene expression in the embryonic thymi of MafB-deficient mice included the reduced expression of Wnt3 and BMP4 in mesenchymal cells and of CCL21 and CCL25 in epithelial cells. These results suggest that MafB expressed in third pharyngeal pouch mesenchymal cells critically regulates lymphocyte accumulation in the embryonic thymus.

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Partial DiGeorge anomaly presenting as an enlarging third pharyngeal pouch cyst

Otolaryngology ◽

10.1016/s0194-5998(95)70022-6 ◽

1995 ◽

Vol 113 (6) ◽

pp. 785-787 ◽

Cited By ~ 1

Author(s):

L DINARDO ◽

D WOHL

Keyword(s):

Pharyngeal Pouch ◽

Digeorge Anomaly ◽

Third Pharyngeal Pouch

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EZH2 is required for parathyroid and thymic development through differentiation of the third pharyngeal pouch endoderm

Disease Models & Mechanisms ◽

10.1242/dmm.046789 ◽

2021 ◽

pp. dmm.046789

Author(s):

Cinzia Caprio ◽

Gabriella Lania ◽

Marchesa Bilio ◽

Rosa Ferrentino ◽

Li Chen ◽

...

Keyword(s):

Embryonic Stem ◽

Mouse Embryonic Stem Cell ◽

Mouse Embryos ◽

Pharyngeal Pouch ◽

Expression Domain ◽

Polycomb Repressive Complex 2 ◽

Thymic Development ◽

Conditional Deletion ◽

Pharyngeal Apparatus

The Ezh2 gene encodes a histone methyltransferase of the Polycomb Repressive Complex 2 that methylates histone H3 lysine 27. In this work we asked whether EZH2 has a role in the development of the pharyngeal apparatus and whether it regulates the expression of the Tbx1 gene, which encodes a key transcription factor required in pharyngeal development. To these ends, we performed genetic in vivo experiments with mouse embryos and we used mouse embryonic stem cell (ESC)-based protocols to probe endoderm and cardiogenic mesoderm differentiation. Results showed that EZH2 occupies the Tbx1 gene locus in mouse embryos, and that suppression of EZH2 was associated with reduced expression of Tbx1 in differentiated mESCs. Conditional deletion of Ezh2 in the Tbx1 expression domain, which includes the pharyngeal endoderm, did not cause cardiac defects but revealed that the gene has an important role in the morphogenesis of the 3rd pharyngeal pouch (PP). We found that in conditionally deleted embryos the 3rd PP was hypoplastic, had reduced expression of Tbx1, lacked the expression of Gcm2, a gene that marks the parathyroid domain, but expressed FoxN1, a gene marking the thymic domain. Consistently, the parathyroids did not develop, and the thymus was hypoplastic. Thus, Ezh2 is required for parathyroid and thymic development, probably through a function in the pouch endoderm. This discovery also provides a novel interpretational key for the finding of Ezh2 activating mutations in hyperparathyroidism and parathyroid cancer.

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