MRC National Institute for Medical Research, London
Science for Health
Thymus migration during organogenesis
21 July 2010
The thymus is a key organ of the immune system. It produces T-lymphocytes which are critical parts of the adaptive immune system. The formation of the thymus in the embryo requires coordinated interactions of multiple cell types, including neural crest (NC) cells, to orchestrate the formation and separation of the developing thymus and its subsequent migration from the third pharyngeal pouch to the thoracic cavity.
The mechanisms that control the various morphogenetic events during early thymus organogenesis are still largely unknown, although some genes have been identified that affect these events. Neural crest-derived mesenchyme has been shown to play an important role. Eph receptors and their ligands, ephrins, are required for a number of developmental processes. A significant number of Eph receptors and ephrin ligands are expressed in the thymus and are known to have immunoregulatory properties.
Dimitris Kioussis (pictured) and his group in the Division of Molecular Immunology in NIMR and Mark Coles' group at the Hull York Medical School worked with David Wilkinson's group in NIMR's Division of Developmental Neurobiology to investigate the role of EphB ephrin-B2 interactions in thymus development.
They showed that, in the absence of ephrin-B2 expression on thymic NC-derived mesenchyme, the thymus remains in the cervical area instead of migrating into the thoracic cavity. Analysis of individual NC-derived thymic mesenchymal cells shows that, in the absence of ephrin-B2, their motility is impaired as a result of defective EphB receptor signaling. This implies a NC-derived cell-specific role of EphB–ephrin-B2 interactions in the collective migration of the thymic rudiment during organogenesis.
Exactly how groups of cells move around the body is still unknown. But, by studying some of the processes involved in organ migration, we have provided useful information to help us to understand, for instance, how tumours spread and wounds heal.
Mark Coles
Histological analyses and Foxn1 and Gcm2 expression
Histological analyses and Foxn1 and Gcm2 expression in E11.5–E13.5 wild-type and Ephrin-B2Lx/Lx;Wnt1-Cre;Rosa26eYfp mutant embryos.
Original article
The research findings are published in full in:
EphB–ephrin-B2 interactions are required for thymus migration during organogenesis (2010)
Katie E. Foster, Julie Gordon, Kim Cardenas, Henrique Veiga-Fernandes, Taija Makinen, Elena Grigorieva, David G. Wilkinson, C. Clare Blackburn, Ellen Richie, Nancy R. Manley, Ralf H. Adams, Dimitris Kioussis, and Mark C. Coles
Proceedings of the National Academy of Sciences of the USA Epub ahead of print. Publisher abstract
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