Immunocytochemical studies using monoclonal antibodies directed against oncogenic peptides revealed a heterogeneous distribution of the peptides within the ventricular zone of the embryonic day 18 rat forebrain. The sis-, src-, ras-, and myc-encoded peptides were concentrated in the same isolated clusters of 5-25 radial glial cells (also identified by vimentin staining), providing a transient columnar compartmentalization to the ventricular zone. An increased number of [3lHlthymidine-labeled ventricular zone cells were observed within the protooncogene stained radial glial cell columns as compared to noncolumn areas. The columnar heterogeneity of radial glial cells reveals the mosaicism of the embryonic ventricular zone and the differential proliferation of its cells.The mammalian telencephalon develops embryonically from the ventricular zone and at later stages from the subventricular zone, which are proliferative regions of the developing brain (1). Within the apparently homogeneous cells of the ventricular zone (2), there are few markers of the commitments made by cells to their eventual differentiated fates (3). Indeed, the question of whether neuronal fate is determined in the ventricular zone or postmitotically (after they migrate out of this zone) is under current debate. Protooncogenes, the cellular homologues of oncogenes, have been shown to be expressed in different stages of embryonic development in a variety of tissues (4, 5). Available evidence suggests that the action of protooncogene products on cells can be to increase mitotic activity and to induce differentiation (6). The purpose of the present study was to determine the distribution of protooncogenes within the developing forebrain of the embryonic rat, as possible markers of selective proliferation or differentiation of brain cells. The involvement of protooncogenes in neuronal development has been previously investigated in the developing cerebellum and retina, where the src oncogene has been localized to postmitotic neurons in both of these structures (7,8).The protooncogenes sis [a homologue of the B chain of platelet-derived growth factor (9)], src [a tyrosine kinase (10)], ras [a GTP binding protein (11)], and myc [a DNA binding protein (12)] represent members of different classes of protooncogenes. In the present study, these protooncogenes were found to be expressed in the same isolated clusters of radial glial cells in the ventricular zone. Although radial glial cells are capable of division (13), some remain mitotically dormant during late embryogenesis (14). Radial glial cells' fibers are thought to aid in the prenatal migration of young postmitotic neurons (15,16). Their cell bodies are juxtaposed to the ventricle and a long process extends to the outer surface of the developing brain (17). The regional and time-dependent expression of certain protooncogenes in specific columns of radial glial cells, along with associated changes in vimentin expression and the proliferation of nearby cells, reveal a heterogeneous organizati...