RT Journal Article SR Electronic T1 A Notch-regulated proliferative stem cell zone in the developing spinal cord is an ancestral vertebrate trait JF bioRxiv FD Cold Spring Harbor Laboratory SP 298877 DO 10.1101/298877 A1 Ricardo Lara-Ramirez A1 Carlos Pérez-González A1 Chiara Anselmi A1 Cedric Patthey A1 Sebastian M. Shimeld YR 2018 UL http://biorxiv.org/content/early/2018/04/11/298877.abstract AB Vertebrates have evolved the most sophisticated nervous systems we know. These differ from the nervous systems of invertebrates in several ways, including the evolution of new cell types, and the emergence and elaboration of patterning mechanisms to organise cells in time and space. Vertebrates also generally have many more cells in their central nervous systems than invertebrates, and an increase in neural cell number may have contributed to the sophisticated anatomy of the brain and spinal cord. Here we study how increased cell number evolved in the vertebrate central nervous system, investigating the regulation of cell proliferation in lampreys as basally-diverging vertebrate, and focusing on the spinal cord because of its relatively simple anatomy. Markers of proliferating cells show that a medial proliferative progenitor zone is found throughout the lamprey spinal cord. We show that inhibition of Notch signalling disrupts the maintenance of this proliferative zone. When Notch signalling is blocked progenitor cells differentiate precociously, the proliferative medial zone is lost, and differentiation markers activate throughout the medial-lateral axis of the spinal cord. Comparison to other chordates suggests that the emergence of a persistent Notch-regulated proliferative progenitor zone in the medial spinal cord of vertebrate ancestors was a critical step for the evolution of the vertebrate spinal cord and its complexity.Summary statement Vertebrates develop nervous systems with numerous cells. Study of cell proliferation in the lamprey nervous system links this to a medial proliferation zone regulated by Notch signalling, a vertebrate innovation.