ENVIRONMENTAL SIGNALS INFLUENCE EXPRESSION OF A CORTICAL AREAL PHENOTYPE IN-VITRO INDEPENDENT OF EFFECTS ON PROGENITOR-CELL PROLIFERATION

We have shown previously that, in vitro, cortical progenitor cells iso lated from specific locations of the cerebral wall can adopt area-spec ific fates, assayed by expression of the limbic system-associated memb rane protein (LAMP; R. T. Ferri and P. Levitt, Cereb. Cortex 3, 187-19 8, 1993). Progenitors destined to produce LAMP neurons, however, will differentiate to express the limbic: molecular phenotype if grown with TGF alpha and collagen type IV (R. T. Ferri and P. Levitt, Developmen t 121, 1151-1160, 1995), while other signals fail to induce LAMP. The present study used BrdU labeling of progenitor cells to examine whethe r modulation of LAMP expression was paralleled by predictable changes in cell proliferation. The general pattern of proliferation is similar under a variety of culture conditions: approximately half the cells a re mitotic, and activity is always highest during the first 24 hr in v itro, with little cell division occurring by the third day. Moreover, the rate of proliferation, in the presence or absence of TGF alpha, is the same on all substrates tested, with the exception of laminin. The TGF alpha/collagen type IV signaling system that induces LAMP express ion by the precursors has no modulating effect on their proliferative kinetics. Nonetheless, only progenitors that are mitotically active re spond to LAMP-inducing signals; only 60% of the neurons, representing those that have divided at least once in culture, can be induced to ex press LAMP. The data suggest that while specific signals affect choice of area phenotype during the cell cycle, they do so in the absence of major changes in proliferative behavior. (C) 1996 Academic Press, Inc .