Constitutively active Notch1 converts cranial neural crest-derived frontonasal mesenchyme to perivascular cells in vivo

Abstract

Perivascular/mural cells originate from either the mesoderm or the cranial neural crest. Regardless of their origin, Notch signalling is necessary for their formation. Furthermore, in both chicken andmouse, constitutive Notch1 activation (via expression of theNotch1 intracellular domain) is sufficient in vivo to convert trunk mesoderm-derived somite cells to perivascular cells, at the expense of skeletal muscle. In experiments originally designed to investigate the effect of premature Notch1 activation on the development of neural crest-derived olfactory ensheathingglial cells (OECs),we usedinovo electroporation to inserta tetracycline-inducible NotchδE construct (encoding a constitutively active mutant of mouse Notch1) into the genome of chicken cranial neural crest cell precursors, and activated Notch'E expression by doxycycline injection at embryonic day 4. NotchδE-targeted cells formed perivascular cells within the frontonasal mesenchyme, and expressed a perivascular marker on the olfactory nerve. Hence, constitutively activating Notch1 is sufficient in vivo to drive not only somite cells,but alsoneural crest-derivedfrontonasalmesenchyme and perhapsdevelopingOECs, toa perivascularcell fate.Theseresults also highlight the plasticity of neural crest-derived mesenchyme and glia.