Thymus Development

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Embryonic origins of the endocrine organs of the neck
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.

The thymic medulla phagocytes negatively selects auto reactive CD4+ and CD8+ thymocytes, eliminate T cells bearing autoreactive T cell antigen receptors (TCRs). This process to prevent autoimmunity is also known as "negative selection", see adult thymus T cell elimination movie.

Endocrine Links: Introduction | BGD Lecture | Science Lecture | Pineal | Hypothalamus‎ | Pituitary | Thyroid | Parathyroid | Thymus‎ | Pancreas‎ | Adrenal‎ | Gonad‎ | Placenta‎ | Other Tissues | Stage 22 | Abnormalities | Hormones | Category:Endocrine

Immune Links: Introduction | Blood | Spleen | Thymus | Lymphatic | Lymph Node | Antibody | Med Lecture - Lymphatic Structure | Med Practical | Immune Movies | Vaccination | Bacterial Infection | Category:Immune
Historic Embryology
1912 Development of the Lymphatic System | 1918 Gray's Lymphatic Images | 1916 Pig Lymphatics | 1919 Chicken Lymphatic | 1922 Pig Stomach Lymphatics | Historic Disclaimer

Some Recent Findings

Mouse Thymus gene expression[1]
  • Multiple roles for HOXA3 in regulating thymus and parathyroid differentiation and morphogenesis in mouse[2] "Previous studies have shown that the Hoxa3 null mutant lacks third pharyngeal pouch derivatives, the thymus and parathyroids by E18.5, and organ-specific markers are absent or downregulated during initial organogenesis. Our current analysis of the Hoxa3 null mutant shows that organ-specific domains did undergo initial patterning, but the location and timing of key regional markers within the pouch, including Tbx1, Bmp4 and Fgf8, were altered. Expression of the parathyroid marker Gcm2 was initiated but was quickly downregulated and differentiation failed; by contrast, thymus markers were delayed but achieved normal levels, concurrent with complete loss through apoptosis. To determine the cell type-specific roles of Hoxa3 in third pharyngeal pouch development, we analyzed tissue-specific mutants using endoderm and/or neural crest cell (NCC)-specific Cre drivers. Simultaneous deletion with both drivers resulted in athymia at E18.5, similar to the null. By contrast, the individual tissue-specific Hoxa3 deletions resulted in small, ectopic thymi, although each had a unique phenotype. Hoxa3 was primarily required in NCCs for morphogenesis. In endoderm, Hoxa3 temporally regulated initiation of the thymus program and was required in a cell-autonomous manner for parathyroid differentiation. Furthermore, Hoxa3 was required for survival of third pharyngeal pouch-derived organs, but expression in either tissue was sufficient for this function." Developmental Signals - Homeobox
  • Dynamics of thymus organogenesis and colonization in early human development[3] "The thymus is the central site of T-cell development and thus is of fundamental importance to the immune system, but little information exists regarding molecular regulation of thymus development in humans. ... In addition, we provide molecular evidence that the human thymic epithelium derives solely from the third pharyngeal pouch, as in the mouse, in contrast to previous suggestions."
  • Thymus organogenesis[4]"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[5] "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. "
More recent papers
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This table shows an automated computer PubMed search using the listed sub-heading term.
  • Therefore the list of references do not reflect any editorial selection of material based on content or relevance.
  • References appear in this list based upon the date of the actual page viewing.

References listed on the rest of the content page and the associated discussion page (listed under the publication year sub-headings) do include some editorial selection based upon both relevance and availability.

Links: References | Discussion Page | Pubmed Most Recent

Search term: Thymus Embryology

Hai-Bo Huang, Ke Xiao, Shun Lu, Ke-Li Yang, Abdur Rahman Ansari, Haseeb Khaliq, Hui Song, Juming Zhong, Hua-Zhen Liu, Ke-Mei Peng Increased Thymic Cell Turnover under Boron Stress May Bypass TLR3/4 Pathway in African Ostrich. PLoS ONE: 2015, 10(6);e0129596 PMID: 26053067 H Hancı, S Türedi, Z Topal, T Mercantepe, I Bozkurt, H Kaya, Ş Ersöz, B Ünal, E Odacı Can prenatal exposure to a 900 MHz electromagnetic field affect the morphology of the spleen and thymus, and alter biomarkers of oxidative damage in 21-day-old male rats? Biotech Histochem: 2015;1-9 PMID: 25985826 S Ozkanlar, A Kara, E Sengul, N Simsek, A Karadeniz, N Kurt Melatonin Modulates the Immune System Response and Inflammation in Diabetic Rats Experimentally-Induced by Alloxan. Horm. Metab. Res.: 2015; PMID: 25938889 Angelija Valančiūtė, Raminta Mozuraitė, Ingrida Balnytė, Janina Didžiapetrienė, Paulius Matusevičius, Donatas Stakišaitis Sodium valproate effect on the structure of rat glandule thymus: Gender-related differences. Exp. Toxicol. Pathol.: 2015; PMID: 25937562 J P Madej, T Stefaniak, M Bednarczyk Effect of in ovo-delivered prebiotics and synbiotics on lymphoid-organs' morphology in chickens1. Poult. Sci.: 2015; PMID: 25877410

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.

Week 8

Late embryonic thymus development.

Stage 22 image 200.jpg Human- Stage 22 thymus 01.jpg
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
Fetal thymus weight growth graph.jpg

Human Fetal Thymus Weight Growth

Overall Size Changes with age
  • 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

Thymus Histology: Fetal Thymus overview | Fetal Thymus Medulla | Fetal Thymus Cortex | Adult Thymus | unlabeled fetal overview | unlabeled fetal medulla |unlabeled fetal thymic corpuscle |unlabeled fetal cortex | unlabeled adult overview | Category:Thymus | Immune System Development
  • 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)

T Lymphocyte

The following images are electron micrographs of T Lymphocyte (T cell) at different stages.

Lymphocyte EM Images: T and B Lymphocytes 1 TEM | T and B Lymphocytes 2 TEM | T Lymphocyte SEM | B lymphocyte 1 TEM | B lymphocyte 2 TEM | B lymphocyte 3 TEM | Plasma Cell TEM | T2 Lymphocyte 1 TEM | T2 Lymphocyte 2 TEM | lymphocyte rosettes | T lymphocyte 1 | T lymphocyte 2 | T lymphocyte 3 | T lymphocyte 4 | T lymphocyte 5 | T lymphocyte 6 | B lymphocyte | B lymphocytes TEM | Immune System Development | Blood

Thymus Phagocytes

Click Here to play on mobile device

Movie shows how dying thymocytes are efficiently cleared by phagocytes.[6]

Examples of cell death in situ during negative selection.

Purified CD4+CD8+ F5 thymocytes labeled with SNARF and Hoechst were introduced into LysM-GFP thymic slices then treated with 1 nM specific peptide for 30 min.

The incubation was continued for the indicated times and the slices were imaged by time-lapse two-photon microscopy.

The arrowheads point to dy|}ing thymocytes. Scale bars are 5 µm.

Mouse adult thymus 11.jpg

Mouse adult thymus 11.jpg
 ‎‎Thymus 1
Page | Play

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

Thymus adult.jpg

Adult Thymus Histology

A postnatal process defined as a decrease in the size, weight and activity of the gland with advancing age.
  • After puberty much of the parenchyma of the thymus is replaced by adipose tissue.
  • particularly cortical lymphoid tissue.
  • initially proceeds rapid but slows down in adulthood.
  • Increase in size of thymic corpuscles.
  • process is called involution
  • under the control of steroid hormones

In a recent review[7], 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.

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 (1817-1894) a British physician and chemist.


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.[8]

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.[9]


Thymus Histology: Fetal Thymus overview | Fetal Thymus Medulla | Fetal Thymus Cortex | Adult Thymus | unlabeled fetal overview | unlabeled fetal medulla |unlabeled fetal thymic corpuscle |unlabeled fetal cortex | unlabeled adult overview | Category:Thymus | Immune System Development

The developing fetal thymus shown below is from a 20 week gestational age (GA), 18 week post-fertilization age, or second trimester stage of development.

Molecular Development

Mouse Thymus gene expression[1]
Mouse Thymus E9.5 and E10.5[1]
Mouse Thymus E11[1]

Foxg1 and Isl1

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



Cited2 deletion in the mouse is embryonic lethal with cardiovascular malformations, adrenal agenesis, cranial ganglia fusion, exencephaly, and left-right patterning defects.[10]

"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.[11]

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


  1. 1.0 1.1 1.2 1.3 Qiaozhi Wei, Brian G Condie A focused in situ hybridization screen identifies candidate transcriptional regulators of thymic epithelial cell development and function. PLoS ONE: 2011, 6(11);e26795 PMID: 22087235 | PLoS One.
  2. Jena L Chojnowski, Kyoko Masuda, Heidi A Trau, Kirk Thomas, Mario Capecchi, Nancy R Manley Multiple roles for HOXA3 in regulating thymus and parathyroid differentiation and morphogenesis in mouse. Development: 2014, 141(19);3697-708 PMID: 25249461
  3. Alison M Farley, Lucy X Morris, Eric Vroegindeweij, Marianne L G Depreter, Harsh Vaidya, Frances H Stenhouse, Simon R Tomlinson, Richard A Anderson, Tom Cupedo, Jan J Cornelissen, C Clare Blackburn Dynamics of thymus organogenesis and colonization in early human development. Development: 2013, 140(9);2015-26 PMID: 23571219
  4. Qing Ge, Yong Zhao Evolution of thymus organogenesis. Dev. Comp. Immunol.: 2011, 39(1-2);85-90 PMID: 22266420
  5. Hélia Neves, Elisabeth Dupin, Leonor Parreira, Nicole M Le Douarin Modulation of Bmp4 signalling in the epithelial-mesenchymal interactions that take place in early thymus and parathyroid development in avian embryos. Dev. Biol.: 2012, 361(2);208-19 PMID: 22057081
  6. Ivan Lilyanov Dzhagalov, Katherine Grace Chen, Paul Herzmark, Ellen A Robey Elimination of self-reactive T cells in the thymus: a timeline for negative selection. PLoS Biol.: 2013, 11(5);e1001566 PMID: 23700386 | PLoS Biol. | PLoS Biol. Immunobiology Collection
  7. Victor Appay, Delphine Sauce, Martina Prelog The role of the thymus in immunosenescence: lessons from the study of thymectomized individuals. Aging (Albany NY): 2010, 2(2);78-81 PMID: 20354268
  8. Norihiko Watanabe, Yi-Hong Wang, Heung Kyu Lee, Tomoki Ito, Yui-Hsi Wang, Wei Cao, Yong-Jun Liu Hassall's corpuscles instruct dendritic cells to induce CD4+CD25+ regulatory T cells in human thymus. Nature: 2005, 436(7054);1181-5 PMID: 16121185
  9. I Varga, V Pospisilova, V Jablonska, V Sisovsky, P Galfiova, S Polak, M Adamkov Thymic Hassall's bodies of children with congenital heart defects. Bratisl Lek Listy: 2010, 111(10);552-7 PMID: 21125801
  10. Anna C Michell, José Bragança, Carol Broadbent, Bradley Joyce, Angela Franklyn, Jürgen E Schneider, Shoumo Bhattacharya, Simon D Bamforth A novel role for transcription factor Lmo4 in thymus development through genetic interaction with Cited2. Dev. Dyn.: 2010, 239(7);1988-94 PMID: 20549734
  11. Dan Zou, Derek Silvius, Julie Davenport, Raphaelle Grifone, Pascal Maire, Pin-Xian Xu Patterning of the third pharyngeal pouch into thymus/parathyroid by Six and Eya1. Dev. Biol.: 2006, 293(2);499-512 PMID: 16530750


Thomas Boehm, Jeremy B Swann Thymus involution and regeneration: two sides of the same coin? Nat. Rev. Immunol.: 2013, 13(11);831-8 PMID: 24052146

Julie Gordon, Nancy R Manley Mechanisms of thymus organogenesis and morphogenesis. Development: 2011, 138(18);3865-78 PMID: 21862553

Thomas Boehm Thymus development and function. Curr. Opin. Immunol.: 2008, 20(2);178-84 PMID: 18403191

Wilson Savino The thymus is a common target organ in infectious diseases. PLoS Pathog.: 2006, 2(6);e62 PMID: 16846255

Georg Holländer, Jason Gill, Saulius Zuklys, Norimasa Iwanami, Cunlan Liu, Yousuke Takahama Cellular and molecular events during early thymus development. Immunol. Rev.: 2006, 209;28-46 PMID: 16448532

Thomas Boehm, Conrad C Bleul, Michael Schorpp Genetic dissection of thymus development in mouse and zebrafish. Immunol. Rev.: 2003, 195;15-27 PMID: 12969307

J Sen Signal transduction in thymus development. Cell. Mol. Biol. (Noisy-le-grand): 2001, 47(1);197-215 PMID: 11292256


Adrienne E Calder, Melanie N Hince, Jarrod A Dudakov, Ann P Chidgey, Richard L Boyd Thymic involution: where endocrinology meets immunology. Neuroimmunomodulation: 2011, 18(5);281-9 PMID: 21952680

A Cromi, F Ghezzi, R Raffaelli, V Bergamini, G Siesto, P Bolis Ultrasonographic measurement of thymus size in IUGR fetuses: a marker of the fetal immunoendocrine response to malnutrition. Ultrasound Obstet Gynecol: 2009, 33(4);421-6 PMID: 19306477

Yaron Zalel, Ronni Gamzu, Shlomo Mashiach, Reuven Achiron The development of the fetal thymus: an in utero sonographic evaluation. Prenat. Diagn.: 2002, 22(2);114-7 PMID: 11857615

Search PubMed: Thymus Development | Thymus Embryology


  • Cytotoxic T lymphocytes - (CTLs, killer T cells) directly attack other cells carrying certain foreign or abnormal molecules on their surfaces including attacking viruses, that hide from other parts of the immune system growing inside infected cells.
  • Helper T cells - (Th cells) coordinate immune responses by communicating with other cells. Some stimulate nearby B cells to produce antibodies, others call in phagocytes, and still others activate other T cells.

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Cite this page: Hill, M.A. (2015) Embryology Thymus Development. Retrieved July 7, 2015, from

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