A Notch-regulated proliferative stem cell zone in the developing spinal cord is an ancestral vertebrate trait

Abstract

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 the lamprey spinal cord. Markers of proliferation show that a ventricular progenitor zone is found throughout the lamprey spinal cord. We show that inhibition of Notch signalling disrupts the maintenance of this zone. When Notch is blocked, progenitor cells differentiate precociously, the proliferative ventricular zone is lost and differentiation markers become expressed throughout the spinal cord. Comparison with other chordates suggests that the emergence of a persistent Notch-regulated proliferative progenitor zone was a crucial step for the evolution of vertebrate spinal cord complexity.

Step-wise evolution of neural patterning by Hedgehog signalling in chordates

“…Since in vertebrates repression is mediated by cross repression between Class I and Class II genes, the evolution of such interactions may underlie this change in patterning. This period of evolution also coincides with the evolution of a large pool of progenitors in the ventricular zone along the length of the vertebrate neural tube 31 , and it is in these progenitors that these and other Hh-regulated Class I and II genes interact to define the DV progenitor zones from which differentiating cells emerge. Further experiments may reveal which of these interactions might also have evolved in early vertebrates, and more precisely show how changes in Hh-regulated patterning map on to the evolution of vertebrate nervous systems and their nuanced control of behaviour 11 .…”

Key Steps in the Evolution of Mammalian Movement: A Prolegomenal Essay

“…The VZ comprises a population of medial cells along the lumen of the central canal; these cells are in a proliferative progenitor state ( Lara-Ramirez et al, 2019 ). The geometry of this “tube” of progenitor cells is such that the cells are exposed to morphogens, and differentiate based on Cartesian signal gradients (recognising, of course, that this is an oversimplification – see Gouti et al (2015) ).…”

Evolution of vertebrate spinal cord patterning

“…46 Notch in the ventricular zone in vertebrates and in the tailbud in amphioxus. References: Gnathostomes; Mouse, 47 ; Chick, 48 ; Zebrafish, ventricular zone notch and delta 49,50 ; Lamprey 11,45 ; Amphioxus. 51 RA from vertebrate somites and roof plate in gnathostomes and dorsal neurons in lamprey, 52 no data in amphioxus.…”

“…Lamprey embryos do, and resemble jawed vertebrates with a well-defined progenitor cell zone visible both by cell morphology and gene expression in brain and spinal cord. 11,45 The mechanism is conserved, since Notch signaling maintains progenitor cells at the ventricular zone, with inhibition of Notch by DAPT causing loss of progenitor cell markers PCNA, OligA, and HesB, and premature differentiation as seen by gain of the differentiation markers CoeA and CoeB. 11 With their highly reduced posterior CNS, sea squirt embryos do not have cells comparable to the ventricular progenitors of jawed vertebrates.…”