A subpopulation of somitic cells that are activated for Notch migrate to and invade the primary dorsal aorta, where they eventually occupy the entire endothelial tissue.

Image courtesy of Dr Yoshiko Takahashi, Nara Institute of Science and Technology, Japan.

The formation of primary blood vessels involves endothelial cell differentiation, tubule formation and three-dimensional vessel assembly. In Developmental Cell, Yoshiko Takahashi and colleagues now report that the highly conserved Notch signalling pathway is responsible for the specification of somitic cells into aortic endothelium and for their assembly into the dorsal aorta - the first embryonic vessel that forms.

To understand the role of Notch in aortic formation, the authors first identified 'Notch-active' cells by electroporating a Notch signal-detecting reporter plasmid (pTP1-Venus) into chick embryo mesodermal cells. They found that Venus-positive cells were initially located in the posterior edge of individual somites, but then migrated ventrally to become integrated into the dorsal aorta.

A constitutively active form of Notch was introduced into cells that were randomly distributed in developing somites, causing the cells to become gradually confined to the posterior edge of each somite. This posterior location was lost when the Notch signal was inactivated, showing that Notch signalling is both necessary and sufficient to direct the specification of aortic precursors in the posterior half of individual somites.

'Notch-activated' cells migrated ventrally and participated in the formation of the dorsal aorta. When grafted to ectopic locations, only Notch-activated cells were able to migrate to the target destination and become incorporated into the endothelial component of the aorta. Moreover, aortic grafting specifically attracted Notch-activated cells. Together, these results show that migration is dependent upon Notch activity and that the dorsal aorta produces attractive signals that promote the directed migration of Notch-activated endothelial precursors.

The signalling molecule EphrinB2 is known to be important for mediating Notch-dependent arterial differentiation. The authors tested whether EphrinB2 was required for Notch function in migration and found that EphrinB2 expression caused cells to behave as if Notch was activated, and EphrinB2 depletion prevented migration. Thus, EphrinB2 acts downstream of Notch and is necessary for Notch-activated cells to migrate ventrally.

Yoshiko Takahashi and colleagues also showed that at the later stage of development, Notch-positive endothelial precursors that originate from posterior somites spread along the anterior-posterior and dorso-ventral axes of the aorta. This replaces existing cells of splanchnic origin, which in turn differentiate into haematopoietic cells.

Author: Kim Baumann