Thymus Development

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.

Some Recent Findings

Thymus organogenesis "A new study in the jawless fish, lampreys, indicates the existence of a primitive thymus in these surviving representatives of the most ancient vertebrates, providing strong evidence of co-evolution of T cells and thymus." Modulation of Bmp4 signalling in the epithelial-mesenchymal interactions that take place in early thymus and parathyroid development in avian embryos "Epithelial-mesenchymal interactions are crucial for the development of the endoderm of the pharyngeal pouches into the epithelia of thymus and parathyroid glands. ...Furthermore, mesenchymal-derived Bmp4 appears to be essential to promote early stages of endoderm development during a short window of time, irrespective of the mesenchymal source. In vivo studies using the quail-chick system and implantation of growth factor soaked-beads further showed that expression of Bmp4 by the mesenchyme is necessary during a 24 h-period of time. After this period however, Bmp4 is no longer required and another signalling factor produced by the mesenchyme, Fgf10, influences later differentiation of the pouch endoderm. "

Recent References | References

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.

Thymic epithelial cells (TECs) are derived from the endoderm of the third pharyngeal pouch.

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.

Image shows general position of the developing thymus in entire embryo cross-section. The developing thymus is shown in the midline, located behind the sternum (right) and in front of the oesophagus and trachea.	Selected high power image of thymus from complete cross-section above.

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

Young medulla	Young cortex

Thymic corpuscle

Hassall’s corpuscle - Mass of concentric epithelioreticular cells

Thymus Involution

Adult Thymus

A postnatal process defined as a decrease in the size, weight and activity of the gland with advancing age. In a recent review, 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.

• 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.
• 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.
• features are named after Arthur Hill Hassall|Arthur Hill Hassall (1817-1894) a British physician and chemist.

Function

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.

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.

Molecular Development

Mouse Thymus gene expression

Mouse Thymus E9.5 and E10.5

Mouse Thymus E11

Foxg1 and Isl1

Transcription factors that appear to have a role in early thymic epithelial cell (TEC) differentiation

Cited2

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

"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.

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

References

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, April 18) 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