The oligodendrocyte is the myelin-forming cell in the central nervous system. Despite the close interaction between axons and oligodendrocytes, there is little evidence that neurons influence myelinogenesis. On the contrary, newly differentiated oligodendrocytes, which mature in culture in the total absence of neurons, synthesize the myelinspecific constituents of oligodendrocytes differentiated in vivo and even form myelin-like figures. Neuronal To determine whether the onset of myelination was the consequence only of oligodendrocyte maturation or depended on an axonal signal, we investigated the influence of axonal electrical activity on myelinogenesis. Indeed, action potentials have been demonstrated to play a key role during CNS development, particularly in the visual system (20,21). Here we show that inhibition of electrical activity with the specific Na+ channel blocker tetrodotoxin (TTX) prevents the initiation of myelinogenesis in a system of in vitro myelination using dissociated cultures from embryonic brain and in vivo, in the optic nerve. In addition, with K+ that blocks action potentials by maintaining the cells in a depolarized state, or a-scorpion toxin (a-ScTX), which induces repetitive electrical activity by slowing Na+ channel inactivation, we provide evidence that it is the action potential itself which is responsible for the onset of myelination.

Objective-Circulating progenitors and stem cells have been reported to contribute to angiogenesis and arterial repair after injury. In the present study, we investigated whether the arterial wall could host permanently residing progenitor cells under physiological context. Methods and Results-Using the Hoechst-based flow cytometry method, we identified and isolated progenitor cells termed side population (SP) cells at a prevalence of 6.0Ϯ0.8% in the tunica media of adult mice aortas. Arterial SP cells expressed the ATP-binding cassette transporter subfamily G member 2, frequently present on SP cell surface, and displayed a Sca-1 ϩ c-kit -/low Lin Ϫ CD34 Ϫ/low profile. They did not form myeloid or lymphoid hematopoietic colonies after plating in methylcellulose-based medium. Importantly, cultured SP cells were able to acquire the phenotype of endothelial cells (CD31, VE-cadherin, and von Willebrand factor expression) or of smooth muscle cells (␣-smooth muscle actin, calponin, and smooth muscle myosin heavy chain expression), in presence of either vascular endothelial growth factor or transforming growth factor (TGF)-␤1/PDGF-BB, respectively. Moreover, they generated vascular-like branching structures, composed of both VE-cadherin ϩ cells and ␣-smooth muscle actin ϩ cells on Matrigel. Conclusions-In this study, we provide the first evidence to our knowledge that in the adult mice, the normal arterial wall harbors SP cells with vascular progenitor properties.