The role of neural crest cells in the development, organisation and migration of the thymus

Neural Crest (NC) derived mesenchyme has previously been shown to play an important role in the early development of the foetal thymus. Using Wnt1-Cre and Sox10-Cre mice crossed to Rosa26eYfp reporter mice, NC derived mesenchymal cells were revealed in the adult murine thymus. It is reported here that NC derived cells infiltrate the thymus before E13.5, and differentiate into cells with characteristics of smooth muscle cells associated with large vessels, and pericytes associated with capillaries. In the adult organ at three months of age, NC derived perivascular cells continue to be associated with the vasculature providing structural support to the blood vessels and possibly regulating endothelial cell function. Thymus organogenesis requires co-ordinated interactions of multiple cell types including NC cells that orchestrate the formation, separation and subsequent migration of the developing thymus from the third pharyngeal pouch to the thoracic cavity. The molecular mechanisms driving these processes are unclear, however NC derived mesenchyme has been shown to be important. Here, it is shown that the separation process of the thymus from the pouch is independent of ephrin-B2 expression on thymic NC derived mesenchyme, however in its absence the thymus remains in the cervical area instead of migrating into the thoracic cavity. Analyses of individual NC derived thymic mesenchymal cells shows that the absence of ephrin-B2 impairs their polarisation, and thus motility, as a result of defective EphB receptor signalling. This implies a NC derived cell specific role of EphB-ephrin-B2 interactions in the collective migration of the thymic rudiment during organogenesis