Thymus Development: Difference between revisions

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==Molecular Development==
==Molecular Development==
[[File:Mouse thymus development 02.jpg|thumb|Mouse Thymus gene expression]]
[[File:Mouse thymus development 02.jpg|thumb|Mouse Thymus gene expression<ref name="PMID22087235"<pubmed>22087235</pubmed>| [http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0026795 PLoS One.]</ref>]]
[[File:Mouse thymus development 01.jpg|thumb|Mouse Thymus E9.5 and E10.5]]
[[File:Mouse thymus development 01.jpg|thumb|Mouse Thymus E9.5 and E10.5<ref name="PMID22087235" />]]
[[File:Mouse thymus development 03.jpg|thumb|Mouse Thymus E11]]
[[File:Mouse thymus development 03.jpg|thumb|Mouse Thymus E11<ref name="PMID22087235" />]]
===Cited2===
===Cited2===



Revision as of 14:27, 20 February 2012

Introduction

Adult thymus location

The thymus has a key role in the development of an effective immune system as well as an endocrine function.

The thymus has two origins for the lymphoid thymocytes and the thymic epithelial cells. The thymic epithelium begins as two flask-shape endodermal diverticula that form from the third pharyngeal pouch and extend lateralward and backward into the surrounding mesoderm and neural crest-derived mesenchyme in front of the ventral aorta. The immune system T cells are essential for responses against infections and much research concerns the postnatal development of T cells within the thymus.

The mature thymus epithelium has two main cell types: cortical thymic epithelial (cTECs) and medullary thymic epithelial cells (mTECs) or stromal cells. These thymic stromal cells provide signals for T cell differentiation.

Endocrine Links: Introduction | BGD Lecture | Science Lecture | Lecture Movie | pineal | hypothalamus‎ | pituitary | thyroid | parathyroid | thymus | pancreas | adrenal | endocrine gonad‎ | endocrine placenta | other tissues | Stage 22 | endocrine abnormalities | Hormones | Category:Endocrine
Historic Embryology - Endocrine  
1903 Islets of Langerhans | 1903 Pig Adrenal | 1904 interstitial Cells | 1908 Pancreas Different Species | 1908 Pituitary | 1908 Pituitary histology | 1911 Rathke's pouch | 1912 Suprarenal Bodies | 1914 Suprarenal Organs | 1915 Pharynx | 1916 Thyroid | 1918 Rabbit Hypophysis | 1920 Adrenal | 1935 Mammalian Hypophysis | 1926 Human Hypophysis | 1927 Adrenal | 1927 Hypophyseal fossa | 1930 Adrenal | 1932 Pineal Gland and Cysts | 1935 Hypophysis | 1935 Pineal | 1937 Pineal | 1935 Parathyroid | 1940 Adrenal | 1941 Thyroid | 1950 Thyroid Parathyroid Thymus | 1957 Adrenal
Immune Links: immune | blood | spleen | thymus | lymphatic | lymph node | Antibody | Med Lecture - Lymphatic Structure | Med Practical | Immune Movies | vaccination | bacterial infection | Abnormalities | Category:Immune
Historic Embryology  
1909 Lymph glands | 1912 Development of the Lymphatic System | 1918 Gray's Lymphatic Images | 1916 Pig Lymphatics | 1919 Chicken Lymphatic | 1921 Spleen | 1922 Pig Stomach Lymphatics | 1932 Cat Pharyngeal Tonsil | Historic Disclaimer

Some Recent Findings

  • Rodewald HR. Thymus organogenesis. Annu Rev Immunol. 2008;26:355-88.
  • Boehm T, Bleul CC. The evolutionary history of lymphoid organs. Nat Immunol. 2007 Feb;8(2):131-5. "During vertebrate evolution, primary lymphoid organs appeared earlier than secondary lymphoid organs. Among the sites of primary lymphopoiesis during evolution and ontogeny, those for B cell differentiation have differed considerably, although they often have had myelolymphatic characteristics. In contrast, only a single site for T cell differentiation has occurred, exclusively the thymus."
  • Assarsson E, Chambers BJ, Hogstrand K, Berntman E, Lundmark C, Fedorova L, Imreh S, Grandien A, Cardell S, Rozell B, Ljunggren HG. Severe defect in thymic development in an insertional mutant mouse model. J Immunol. 2007 Apr 15;178(8):5018-27.

Development Overview

Stage 13 Embryo pharyngeal arches showing 3rd pharyngeal pouch

The thymus and parathyroid are derived from 3rd pharyngeal pouches.

Development is a series of epithelial/mesenchymal inductive interactions between neural crest-derived arch mesenchyme and pouch endoderm. There is also the possibility that the surface ectoderm of 3rd pharyngeal clefts participates in thymus development.

Hassall's bodies form between 6 and 10 lunar months in humans. They appear after lymphopoiesis has been established and the cortex, medulla and the cortico-medullary junction are able to select of T lymphocytes undergoing progressive maturation. (Text modified from Bodey and Kaiser, 1997)

Experimental studies have shown that a neural crest contribution is also required during early thymic organogenesis.


MBoC Figure 24-6. The development and activation of T and B cells

Figure 24-7. Electron micrographs of nonactivated and activated lymphocytes

Week 8

Late embryonic thymus development.

Stage 22 image 200.jpg Human- Stage 22 thymus 01.jpg


Links: Carnegie stage 22

Development Changes

Fetal thymus anatomy
Fetal thymus

Changes with age Overall Size

  • birth 10-15 g
  • puberty 30-40 g
  • after puberty - involution
    • Replaced by adipose tissue
    • middle-aged 10 g

Thymus Anatomy

  • Superior mediastinum, anterior to heart
  • Bilobed lymphoepithelial organ
    • Contains reticular cells but no fibers
  • Stem lymphocytes
    • proliferate and differentiate
    • forms long-lived T- lymphocytes

Thymus Cells

  • Reticular cells
    • Abundant, eosinophilic, large, ovoid and light nucleus 1-2 nucleoli
    • sheathe cortical capillaries
    • form an epitheloid layer
    • maintain microenvironment for development of T-lymphocytes in cortex (thymic epitheliocytes)
  • Macrophages
    • cortex and medulla
    • difficult to distinguish from reticular cells in H&E
  • Lymphocytes
    • cortex and medulla - more numerous (denser) in cortex
    • majority of them developing T-lymphocytes (= thymic lymphocytes or thymocytes)

Fetal/Young Thymus

Thymus - young 01.jpg Thymus - young 02.jpg
Young medulla Young cortex

Thymic corpuscle

Hassall’s corpuscle - Mass of concentric epithelioreticular cells

Thymus Involution

A postnatal process defined as a decrease in the size, weight and activity of the gland with advancing age. In a recent review[1], thymic involution was described as a result of high levels of circulating sex hormones, in particular during puberty, and a lower population of precursor cells from the bone marrow and finally changes in the thymic microenvironment.

Thymus adult.jpg

Adult Thymus

  • Cortical lymphoid tissue is replaced by adipose tissue
  • Increase in size of thymic corpuscles

Links: Blue Histology - Thymus

Hassall's Bodies

Fetal thymus showing Hassall's body

Hassall's bodies, also called Hassall's corpuscles, form between 6 and 10 lunar months in humans. They appear after lymphopoiesis has been established and the cortex, medulla and the cortico-medullary junction are able to select of T lymphocytes undergoing progressive maturation.Within the thymus their number increases until puberty, then decreases. These features are named after Arthur Hill Hassall (1817-1894) a British physician and chemist.

Function

Thymus Hassall's corpuscle.jpg

Hassall's corpuscles express thymic stromal lymphopoietin (TSLP), suggesting that Hassall's corpuscles have a critical role in dendritic-cell-mediated secondary positive selection of medium-to-high affinity self-reactive T cells, leading to the generation of CD4(+)CD25(+) regulatory T cells within the thymus.[2]

Thymic stromal lymphopoietin is an epithelial cell-derived cytokine expressed in several tissues (skin, gut, lungs, and thymus) that signals through a TSLP receptor (TSLPR). This receptor is a heterodimer of the IL-7 receptor alpha chain and the TSLPR chain.

Disease Association

There has been one report showing changes in Hassall's bodies morphology associated with congenital heart defects.[3]

Molecular Development

Mouse Thymus gene expression[4]
Mouse Thymus E9.5 and E10.5[4]
Mouse Thymus E11[4]

Cited2

Cited2 deletion in the mouse is embryonic lethal with cardiovascular malformations, adrenal agenesis, cranial ganglia fusion, exencephaly, and left-right patterning defects.[5]

"Examination of Lmo4-deficient embryos revealed partially penetrant cardiovascular malformations and hypoplastic thymus. Examination of Lmo4;Cited2 compound mutants indicated that there is a genetic interaction between Cited2 and Lmo4 in control of thymus development. Our data suggest that this may occur, in part, through control of expression of a common target gene, Tbx1, which is necessary for normal thymus development."

Eva and Six

Both Eva and Six have been implicated in thymus development.[6]

  • Eya - human homolog of the Drosophila 'eyes absent' (Eya) gene.
  • Six - vertebrate genes which are homologs of the Drosophila 'sine oculis' (so) gene.

References

  1. <pubmed>20354268 </pubmed>
  2. <pubmed>16121185</pubmed>
  3. <pubmed>21125801</pubmed>
  4. 4.0 4.1 4.2 22087235</pubmed>| PLoS One.
  5. <pubmed>20549734</pubmed>
  6. <pubmed>16530750</pubmed>

Reviews

<pubmed>18403191</pubmed> <pubmed>16846255</pubmed> <pubmed>16448532</pubmed> <pubmed>12969307</pubmed> <pubmed>11292256</pubmed>

Articles

<pubmed>11857615</pubmed>


Search PubMed: Thymus Development | Thymus Embryology


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Cite this page: Hill, M.A. (2024, March 29) Embryology Thymus Development. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Thymus_Development

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© Dr Mark Hill 2024, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G