Angiogenesis in the embryonic CNS: a new twist on an old tale

The central nervous system (CNS) acquires its vasculature by angiogenesis, a process consisting of proliferation of endothelial cells in existing blood vessels or vascular plexuses and leading to formation of new blood vessels. Angiogenesis begins early in CNS development and continues throughout life. Prevailing notions depict CNS angiogenesis as a passive process driven primarily by demands for oxygen and other nutrients by the growing neuronal populations. Thus, although the CNS vasculature develops concomitant with neuronal identities, which emerge under the influence of compartment-specific cell autonomous factors, cell autonomous patterning signals are not considered to instruct vascular development. We have challenged this prevailing notion by showing that angiogenesis in the mouse telencephalon progresses in an orderly, ventral-to-dorsal gradient regulated in a cell-autonomous manner by compartment-specific homeobox transcription factors. These are the same transcription factors that confer compartmental identities on telencephalic neurons and progenitor populations. Thus, the same cell-autonomous, regional patterning signals that regulate development of telencephalic neuronal networks also regulate development of telencephalic vascular networks, underscoring shared mechanisms in CNS vascular and neuronal development. These novel concepts represent a new twist in the intriguing tale of CNS angiogenesis and offer new perspectives on telencephalic regionalization and histogenesis principles.