Developmental Mechanism - Epithelial Mesenchymal Transition

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Introduction

Gastrulation epithelial to mesenchymal transition

The term epithelial mesenchymal transition (EMT) refers to a developmental process where an established epithelium either "breaks down" or "delaminates" allowing cells to leave the epithelium and become connective tissue (mesenchymal) in organisation. This transition can be a permanent change, or a transient event, where the mesenchymal cells may reestablish a new epithelial organisation (mesenchymal epithelial transition).


Epithelial cells (organised cellular layer) which loose their organisation and migrate/proliferate as a mesenchymal cells (disorganised cellular layers) are said to have undergone an Epithelial Mesenchymal Transition (EMT).

Mesenchymal cells, connective tissue-like, that have undergone this process may at a later time and under specific signaling can undergo the opposite process, mesenchyme to epithelia. In development, this process can be repeated several times during tissue differentiation.


Mechanism - "a process, technique, or system for achieving a result".


This process is also studied in carcinogenesis (oncogenesis) or cancer development, where part of this process can be the transformation of an epithelial cell into a mesenchymal cell.[1][2]


Mechanism Links: mitosis | cell migration | epithelial invagination | epithelial mesenchymal transition | mesenchymal epithelial transition | epithelial mesenchymal interaction | morphodynamics | tube formation | apoptosis | autophagy | axes formation | time | molecular

Some Recent Findings

  • Self-organization of a human organizer by combined Wnt and Nodal signalling[3] "In amniotes, the development of the primitive streak and its accompanying 'organizer' define the first stages of gastrulation. Although these structures have been characterized in detail in model organisms, the human primitive streak and organizer remain a mystery. When stimulated with BMP4, micropatterned colonies of human embryonic stem cells self-organize to generate early embryonic germ layers 1 . Here we show that, in the same type of colonies, Wnt signalling is sufficient to induce a primitive streak, and stimulation with Wnt and Activin is sufficient to induce an organizer, as characterized by embryo-like sharp boundary formation, markers of epithelial mesenchymal transition and expression of the organizer-specific transcription factor GSC. Moreover, when grafted into chick embryos, human stem cell colonies treated with Wnt and Activin induce and contribute autonomously to a secondary axis while inducing a neural fate in the host."
  • p53 coordinates cranial neural crest cell growth and epithelial-mesenchymal transition/delamination processes[4] "Neural crest development involves epithelial-mesenchymal transition (EMT), during which epithelial cells are converted into individual migratory cells. Notably, the same signaling pathways regulate EMT function during both development and tumor metastasis. p53 plays multiple roles in the prevention of tumor development; however, its precise roles during embryogenesis are less clear. We have investigated the role of p53 in early cranial neural crest (CNC) development in chick and mouse embryos. In the mouse, p53 knockout embryos displayed broad craniofacial defects in skeletal, neuronal and muscle tissues. In the chick, p53 is expressed in CNC progenitors and its expression decreases with their delamination from the neural tube. Stabilization of p53 protein using a pharmacological inhibitor of its negative regulator, MDM2, resulted in reduced SNAIL2 (SLUG) and ETS1 expression, fewer migrating CNC cells and in craniofacial defects."
More recent papers  
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Search term: Epithelial Mesenchymal Transition

<pubmed limit=5>Epithelial Mesenchymal Transition</pubmed>

Gastrulation

Links: gastrulation

Neural Crest Development

Early neural crest cell development migration involves an initial epithelial mesenchymal transition to delaminate from the ectoderm layer.[5])


Links: neural crest

Heart Development

During heart development endocardial and epicardial cells produce non-cardiomyocyte lineages undergo rounds of epithelial to mesenchymal transition, see review.[6]


Links: Cardiovascular System Development

Palate Development

During the embryonic period the primary palate fusion, between maxillary process and the frontonasal prominence, requires loss of the epithelial seam.

Human Primary Palate
  • develops between embryonic stages 15 and 18.[7]
  • fusion in the human embryo between stage 17 and 18, from an epithelial seam to the mesenchymal bridge.
Stage17-18 Primary palate.gif
Links: palate

Respiratory Development

Neonatal Human Fetal Rabbit
Neonatal human pulmonary neuroendocrine cell EM01.jpg Fetal rabbit neuroepithelial body 01.jpg
Pulmonary neuroendocrine cell (EM)[8] Neuroepithelial body[8]

Pulmonary Neuroendocrine Cells (PNECs) differentiate in the airway epithelium in late embryonic to early fetal period.[9][10] Later in the mid-fetal period clusters of these cells form neuroepithelial bodies (NEBs). The cells migrate to to form these clusters by a process involving transient epithelial to mesenchymal transition. The process of migration has recently been described as “slithering”[11], where the cells transiently lose epithelial characteristics but remain associated with the membrane while traversing neighboring epithelial cells to reach cluster sites.


Links: Endocrine Respiratory | respiratory


Mesenchymal-to-Epithelial Transition

The alternate process involves the conversion of the embryonic connective tissue organization (mesenchyme) to an epithelial organization (epithelium) that can occur during developmental processes.

This process can be seen occurring during early somitogenesis.


It is also suggested that this mechanism occurs in the maternal uterus during endometrial regeneration following decidualization.[12][13]


Links: Mesenchymal Epithelial Transition

References

  1. Savagner P. (2010). The epithelial-mesenchymal transition (EMT) phenomenon. Ann. Oncol. , 21 Suppl 7, vii89-92. PMID: 20943648 DOI.
  2. Tseng CH, Murray KD, Jou MF, Hsu SM, Cheng HJ & Huang PH. (2011). Sema3E/plexin-D1 mediated epithelial-to-mesenchymal transition in ovarian endometrioid cancer. PLoS ONE , 6, e19396. PMID: 21559368 DOI.
  3. Martyn I, Kanno TY, Ruzo A, Siggia ED & Brivanlou AH. (2018). Self-organization of a human organizer by combined Wnt and Nodal signalling. Nature , 558, 132-135. PMID: 29795348 DOI.
  4. Rinon A, Molchadsky A, Nathan E, Yovel G, Rotter V, Sarig R & Tzahor E. (2011). p53 coordinates cranial neural crest cell growth and epithelial-mesenchymal transition/delamination processes. Development , 138, 1827-38. PMID: 21447558 DOI.
  5. Szabó A & Mayor R. (2018). Mechanisms of Neural Crest Migration. Annu. Rev. Genet. , 52, 43-63. PMID: 30476447 DOI.
  6. von Gise A & Pu WT. (2012). Endocardial and epicardial epithelial to mesenchymal transitions in heart development and disease. Circ. Res. , 110, 1628-45. PMID: 22679138 DOI.
  7. Diewert VM & Lozanoff S. (1993). A morphometric analysis of human embryonic craniofacial growth in the median plane during primary palate formation. J. Craniofac. Genet. Dev. Biol. , 13, 147-61. PMID: 8227288
  8. 8.0 8.1 DiAugustine RP & Sonstegard KS. (1984). Neuroendocrinelike (small granule) epithelial cells of the lung. Environ. Health Perspect. , 55, 271-95. PMID: 6376101
  9. Cutz E. (1982). Neuroendocrine cells of the lung. An overview of morphologic characteristics and development. Exp. Lung Res. , 3, 185-208. PMID: 6188605
  10. Cutz E, Gillan JE & Bryan AC. (1985). Neuroendocrine cells in the developing human lung: morphologic and functional considerations. Pediatr. Pulmonol. , 1, S21-9. PMID: 3906540
  11. Kuo CS & Krasnow MA. (2015). Formation of a Neurosensory Organ by Epithelial Cell Slithering. Cell , 163, 394-405. PMID: 26435104 DOI.
  12. Cousins FL, Murray A, Esnal A, Gibson DA, Critchley HO & Saunders PT. (2014). Evidence from a mouse model that epithelial cell migration and mesenchymal-epithelial transition contribute to rapid restoration of uterine tissue integrity during menstruation. PLoS ONE , 9, e86378. PMID: 24466063 DOI.
  13. Patterson AL, Zhang L, Arango NA, Teixeira J & Pru JK. (2013). Mesenchymal-to-epithelial transition contributes to endometrial regeneration following natural and artificial decidualization. Stem Cells Dev. , 22, 964-74. PMID: 23216285 DOI.


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Mechanism Links: mitosis | cell migration | epithelial invagination | epithelial mesenchymal transition | mesenchymal epithelial transition | epithelial mesenchymal interaction | morphodynamics | tube formation | apoptosis | autophagy | axes formation | time | molecular


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Cite this page: Hill, M.A. (2019, September 24) Embryology Developmental Mechanism - Epithelial Mesenchymal Transition. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Developmental_Mechanism_-_Epithelial_Mesenchymal_Transition

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© Dr Mark Hill 2019, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G