Cardiovascular System - Spleen Development

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Developing Human Spleen (stage 22)

The spleen is located on the left side of the abdomen and has a role initially in blood and then immune system development. The spleen's haematopoietic function (blood cell formation) is lost with embryo development and lymphoid precursor cells migrate into the developing organ. Vascularization of the spleen arises initially by branches from the dorsal aorta. Mesoderm within the dorsal mesogastrium form a long strip of cells adjacent to the forming stomach above the developing pancreas.

The human spleen arises in week 5 within the dorsal mesentery as proliferating mesenchyme overlying the dorsal pancreatic endoderm. Cells required for its hemopoietic function arise from the yolk sac wall and near dorsal aorta. The spleen generates both red and white cells in the 2nd trimester.

Cardiovascular Links: cardiovascular | Heart Tutorial | Lecture - Early Vascular | Lecture - Heart | Movies | 2016 Cardiac Review | heart | coronary circulation | heart valve | heart rate | Circulation | blood | blood vessel | blood vessel histology | heart histology | Lymphatic | ductus venosus | spleen | Stage 22 | cardiovascular abnormalities | OMIM | 2012 ECHO Meeting | Category:Cardiovascular
Historic Embryology - Cardiovascular 
1902 Vena cava inferior | 1905 Brain Blood Vessels | 1909 Cervical Veins | 1909 Dorsal aorta and umbilical veins | 1912 Heart | 1912 Human Heart | 1914 Earliest Blood-Vessels | 1915 Congenital Cardiac Disease | 1915 Dura Venous Sinuses | 1916 Blood cell origin | 1916 Pars Membranacea Septi | 1919 Lower Limb Arteries | 1921 Human Brain Vascular | 1921 Spleen | 1922 Aortic-Arch System | 1922 Pig Forelimb Arteries | 1922 Chicken Pulmonary | 1923 Head Subcutaneous Plexus | 1923 Ductus Venosus | 1925 Venous Development | 1927 Stage 11 Heart | 1928 Heart Blood Flow | 1935 Aorta | 1935 Venous valves | 1938 Pars Membranacea Septi | 1938 Foramen Ovale | 1939 Atrio-Ventricular Valves | 1940 Vena cava inferior | 1940 Early Hematopoiesis | 1941 Blood Formation | 1942 Truncus and Conus Partitioning | Ziegler Heart Models | 1951 Heart Movie | 1954 Week 9 Heart | 1957 Cranial venous system | 1959 Brain Arterial Anastomoses | Historic Embryology Papers | 2012 ECHO Meeting | 2016 Cardiac Review | Historic Disclaimer

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

  • Morphogenesis of the spleen during the human embryonic period[1] "Between Carnegie stages (CSs) 14 and 17, the spleen was usually recognized as a bulge in the dorsal mesogastrium (DM), and after CS 20, the spleen became apparent. Intrasplenic folds were observed later. A high-density area was first recognized in 6 of the 58 cases at CS 16 and in all cases examined after CS 18. The spleen was recognized neither as a bulge nor as a high-density area at CS 13. The mesothelium was pseudostratified until CS 16 and was replaced with high columnar cells and then with low columnar cells. The basement membrane was obvious after CS 17. The mesenchymal cells differentiated from cells in the DM, and sinus formation started at CS 20. Hematopoietic cells were detected after CS 18. The vessels were observed at CS 14 in the DM. Hilus formation was observed after CS 20. The parallel entries of the arteries and veins were observed at CS 23. The rate of increase in spleen length in relation to that of stomach length along the cranial-caudal direction was 0.51 ± 0.11, which remained constant during CSs 19 and 23, indicating that their growths were similar." Kyoto Collection
  • White pulp and marginal zone in human spleen from the 17th to 40th week of gestation[2]
  • Spleen versus pancreas[3] "During early stages of pancreatic development, the mesenchyme that contributes to the spleen overlies the dorsal pancreatic endoderm. Here, we show that interactions between splenic mesenchyme and pancreas proceed via a highly orchestrated morphogenetic program. ...Similar transformations occur in organ cultures employing wild-type pancreatic endoderm and spleen mesenchyme, revealing the developmental plasticity of the pancreas and that precise spatial and temporal control of tissue interactions are required for development of both organs."
  • Fetal and early post-natal development of the human spleen[4] "Immunohistological analysis of 31 human spleens from the 11th week of gestation to the early postnatal period suggested that fetal organ development may be preliminarily divided into four stages."
  • Lymphoid organ development[5] "... At one end are the 'canonical' secondary lymphoid organs, including lymph nodes and spleen; at the other end are 'ectopic' or tertiary lymphoid organs, which are cellular accumulations arising during chronic inflammation by the process of lymphoid neogenesis."
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Search term: Spleen Development

<pubmed limit=5>Spleen+Development</pubmed>

Development Overview

Embryonic Timeline

Stage 13 image 074.jpg Embryonic Carnegie stage data from a recent study of the Kyoto Collection embryos.[1]

Kyoto Collection

D4 Dorsal Mesogastrium (stage 13)

Fetal Timeline

Fetal data from study from week 15 (GA 17) to week 38 (GA 40).[2]

  • week 15 (17 GA) - alpha-smooth muscle actin (alpha-SMA)-positive reticulum cells scattered around the arterioles.
  • week 18 to 21 (20 - 23 GA) - alpha-SMA-positive reticulum cells increase in number and began to form a reticular framework. An accumulation of T and B lymphocytes occurred within the framework, and a primitive white pulp was observed around the arterioles.
  • week 22 (24 GA) - antigenic diversity of the reticular framework was observed, and T and B lymphocytes were segregated in the framework. T lymphocytes were sorted into the alpha-SMA-positive reticular framework, and the periarteriolar lymphoid sheath (PALS) was formed around the arteriole. B lymphocytes aggregated in eccentric portions to the PALS and formed the lymph follicle (LF). The reticular framework of the LF was alpha-SMA-negative.
  • week 24 (26 GA) - marginal zone appeared in the alpha-SMA-positive reticular framework around the white pulp.

(Note - weeks above are approximate post-conception PC corrected from gestational age GA[2])

Reticular framework of white pulp and marginal zone.[2]

"The antigenic heterogeneity of the reticular framework of the white pulp (WP) and marginal zone (MZ) is well documented in the human adult spleen. The ontogeny of the WP and MZ of human fetal spleens was examined with special reference to the heterogeneity of the reticular framework. In the spleen of the 17th gestational week (gw), alpha-smooth muscle actin (alpha-SMA)-positive reticulum cells were scattered around the arterioles. From the 20th to 23rd gw, alpha-SMA-positive reticulum cells increased in number and began to form a reticular framework. An accumulation of T and B lymphocytes occurred within the framework, and a primitive WP was observed around the arterioles. At the 24th gw, antigenic diversity of the reticular framework was observed, and T and B lymphocytes were segregated in the framework. T lymphocytes were sorted into the alpha-SMA-positive reticular framework, and the periarteriolar lymphoid sheath (PALS) was formed around the arteriole. B lymphocytes aggregated in eccentric portions to the PALS and formed the lymph follicle (LF). The reticular framework of the LF was alpha-SMA-negative. MZ appeared in the alpha-SMA-positive reticular framework around the WP at the 26th gw. The PALS, LF, and MZ developed with gestational time. The reticular framework of the PALS, LF, and MZ is thus heterogeneous in the fetal spleen, and the development of the heterogeneity is related to the ontogeny of the PALS, LF, and MZ."

Spleen Development Movies

Click Here to play on mobile device

This animation shows the development of the lesser sac associated with the rotation of the stomach and growth of the liver.

This cross-sectional view of the abdomen viewed from above, with dorsal (back) top and ventral (front) bottom of animation.

Later the retroperitoneal position of the developing kidneys is also shown either side of the dorsal (thoracic) aorta.


  • spleen in mesentery
  • stomach endoderm of gastrointestinal tract
  • liver
  • mesentery

Movie Links: MP4 version | Stomach Development | Spleen Development | Liver Development | Gastrointestinal Tract Development | Coelomic Cavity Development | Movies
Lesser sac 01 icon.jpg
 ‎‎Lesser sac
Page | Play
Gastrointestinal Tract Movies
Gastrointestinal Tract Movies  
Mesoderm 001 icon.jpg
 ‎‎Week 3 Mesoderm
Page | Play
Week3 folding icon.jpg
 ‎‎Week 3
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Amnion 001 icon.jpg
 ‎‎Amniotic Cavity
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Endoderm 002 icon.jpg
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Stomach rotation 01 icon.jpg
 ‎‎Stomach Rotation
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Gastrointestinal tract growth 01 icon.jpg
 ‎‎Tract Growth
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Greater omentum 001 icon.jpg
 ‎‎Greater Omentum
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Lesser sac 01 icon.jpg
 ‎‎Lesser sac
Page | Play
Urogenital septum 001 icon.jpg
 ‎‎Urogenital Septum
Page | Play
 ‎‎GIT Stage 13
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 ‎‎GIT Stage 22
Page | Play
Stage23 MRI S04 icon.jpg
 ‎‎Sagittal GIT
Page | Play
 ‎‎GIT Motility
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Gastroschisis 01.jpg
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Omphalocele 01 icon.jpg
Page | Play
Stage 13 (week 5) Stage 22 (week 8) Stage 23 (week 8) GIT Abnormalities Ultrasound

Adult Spleen


Spleen anatomy.jpg


Adult Spleen and ligamentous attachments.


Spleen Development: SH Lecture Spleen | SH Adult Histology | Overview Red and White Pulp | Overview Red and White Pulp | Cords and Sinuses | Reticular Fibre overview | Reticular Fibre detail | unlabeled red and white pulp | unlabeled red pulp and macrophages | unlabeled white pulp germinal centre | unlabeled reticular fibre | unlabeled white pulp reticular | unlabeled red pulp reticular | Structure cartoon | Cartoon and stain | Category:Spleen | Histology Stains | Immune System Development


Mouse E12 Hox 11 expression[6]


The spleen of wild-type (A) embryos is observed as a brown stripe next to the stomach (black arrowhead).[6]

Mouse spleen formation commences normally at E11.5 and Hox 11 gene expression was previously shown as essential for cell survival during spleen development.[7][8]


Mouse spleen capsulin expression.jpg

A subpopulation of splanchnic mesoderm cells in mice expresses this basic helix-loop-helix (bHLH) transcription factor early in spleen organogenesis. This transcription factor is also expressed in mesenchymal cells that encapsulate the epithelial primordia of internal organs.[9]

Capsulin also known as Epicardin, Podocyte-Expressed 1, POD1, TRANSCRIPTION FACTOR 21; TCF21

Links: OMIM



Congenital absence of the spleen is usually accompanied by complex cardiac malformations, malposition and maldevelopment of the abdominal organs, and abnormal lobation of the lungs. There are a range of other spleen anatomical development abnormalities, some of which have no effect and others are very rare.

Congenital Asplenia

Can be due to left/right patterning abnormality or failure of early spleen differentiation.

Splenic Lobulation

Accessory Spleen

Clinically no significant efects in most patients, occur as single or multiple and generally found in autopsy or as an an incidental finding. Thought to occur due to a failure of primordia fusion within the dorsal mesogastrium.


Splenogonadal Fusion

Rare resulting from abnormal fusion of the splenic and gonadal primordia during prenatal development. On the left side and more common in male and adhesion to the gonad, epididymis or ductus deferens and then follows the caudal descent with the gonad. Failure of complete descent can also result in associated intraabdominal cryptorchism.

Two classifications:

  • continuous - orthotopic spleen connects to the gonad with a cord of fibrous or splenic tissue.
  • discontinuous - no connection between the orthotopic spleen and gonad.

(More? Testis Development)

Ectopic Spleen

A very rare abnormality where the spleen can be found anatomically located in a range of places in the abdominal or thoracic cavity.

Wandering Spleen

Connexin-43 involved with abnormal spleen development (cardiac and lung also).


  1. 1.0 1.1 <pubmed>25403423</pubmed>
  2. 2.0 2.1 2.2 2.3 <pubmed>19255788</pubmed>
  3. <pubmed>16912273</pubmed>
  4. <pubmed>17624541</pubmed>
  5. <pubmed>16550197</pubmed>
  6. 6.0 6.1 <pubmed>10449756</pubmed>| PMC22272 | PNAS
  7. <pubmed>7908720</pubmed>
  8. <pubmed>7555717</pubmed>
  9. <pubmed>10944221</pubmed>


<pubmed>17067939</pubmed> <pubmed>16550197</pubmed> <pubmed>15738953</pubmed> <pubmed>15530642</pubmed> <pubmed>14966753</pubmed> <pubmed>10676919</pubmed> <pubmed>7728201</pubmed>

Search PubMed

Search NCBI Bookshelf: Spleen Development

Search PubMed: Search August 2006 "Spleen Development" 13,401 reference articles of which 450 were reviews.

Search term = Spleen Development | Spleen Abnormalities

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Cite this page: Hill, M.A. (2021, February 26) Embryology Cardiovascular System - Spleen Development. Retrieved from

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© Dr Mark Hill 2021, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G