Cell Proliferation in the Developing Mammalian Brain

Abstract

As the neural tube closes, the future brain consists of a single layer of cells that lines the lumen of the tube. The lumen is the developing ventricular system of the brain, and the layer of cells is the ventricular zone (VZ). The proliferating cells of the VZ will either directly or indirectly give rise to all of the cells of the developing central nervous system (CNS). There are four major proliferative populations in the developing brain. The first of these to appear is the ventricular zone, which is the name agreed upon by the Boulder Committee (1970) as part of an effort to standardize and clarify a nomenclature that sometimes did not reflect accurately the known functions of the layers of the developing CNS. At the same time, the Boulder Committee recognized a second proliferative zone, the sub-ventricular zone (SVZ) that develops later in much of the CNS. Two other proliferative populations arise in specific locations and give rise to specific populations of cells. These are the external granule cell layer of the cerebellum and the subhilar proliferative zone in the dentate gyrus. By the end of the developmental period, these four proliferative populations will give rise to all of the cells of the adult brain (with the exception of a small number that migrate into the brain from the periphery, and two of them, the SVZ and the subhilar zone in the dentate gyrus will continue to proliferate and produce neurons destined for limited areas of the nervous system into adulthood. The regulation of proliferation in these four proliferative zones is responsible for producing the right number of cells of the appropriate classes for all of the subdivisions of the CNS. THE VENTRICULAR ZONE The basic cellular organization of the VZ was recognized by both His (1889, 1897, 1904) and Ramon y Cajal (1894, 1909-1911). Both of these giants of the field recognized that the VZ was several cell diameters in thickness and that there were mitotic figures adjacent to the ventricular surface (Fig. 1). His thought that the mitotic figures were "germinal cells" ("Keimzellen") and that after mitotic division one daughter cell remained adjacent to the ventricular surface to divide again whereas the other became a postmitotic "neuroblast" that migrates away from the VZ and eventually develops into a neu-ron. His also thought that the remaining cells of the VZ were a syncytium of "spongioblasts" that give rise to the glial cells of the CNS. Cajal's views were similar to His' in that he also thought that the mitotic figures on the ventricular surface were a separate population of germinal cells that give rise to neuroblasts, but he did not think that the remaining cells of the epithelium, 2