MULTIPOTENT NEURAL PRECURSORS CAN DIFFERENTIATE TOWARD REPLACEMENT OFNEURONS UNDERGOING TARGETED APOPTOTIC DEGENERATION IN ADULT-MOUSE NEOCORTEX

Neurons undergoing targeted photolytic cell death degenerate by apopto sis, Clonal, multipotent neural precursor cells were transplanted into regions of adult mouse neocortex undergoing selective degeneration of layer II/III pyramidal neurons via targeted photolysis. These precurs ors integrated into the regions of selective neuronal death; 15 +/- 7% differentiated into neurons with many characteristics of the degenera ted pyramidal neurons. They extended axons and dendrites and establish ed afferent synaptic contacts. In intact and kainic acid-lesioned cont rol adult neocortex, transplanted precursors differentiated exclusivel y into glia. These results suggest that the microenvironmental alterat ions produced by this synchronous apoptotic neuronal degeneration in a dult neocortex induced multipotent neural precursors to undergo neuron al differentiation which ordinarily occurs only during embryonic corti cogenesis. Studying the effects of this defined microenvironmental per turbation on the differentiation of clonal neural precursors may facil itate identification of factors involved in commitment and differentia tion during normal development, Because photolytic degeneration simula tes some mechanisms underlying apoptotic neurodegenerative diseases, t hese results also suggest the possibility of neural precursor transpla ntation as a potential cell replacement or molecular support therapy f or some diseases of neocortex, even in the adult.