Lineage specification of olfactory neural precursor cells depends on continuous cell interactions.

We transplanted, as a single cell suspension, cells dissociated from the mature and immature olfactory epithelium of rats or TgR(ROSA26)26Sor mice expressing constitutively the LacZ gene into the developing brain (cerebellum, striatum, inferior colliculus, lateral ventricles) of E15 rat fetuses. Grafted cells or their descendants were still present in the central nervous system more than a month after transplantation. Transplanted cells either integrated as isolated cells or, during the first day after transplantation, reaggregated into clusters. Scattered cells, despite their placodal origin, differentiated into neuron or glial cells with a central phenotype. This was demonstrated by anatomical methods and selective amplification of cDNA encoding for neuronal specific transcripts (microtubule-associated protein 2 and middle-molecular-mass neurofilament protein) expressed by the engrafted cells. Cells in large clusters generated an epithelium containing mature olfactory neurons. Some of them were immunoreactive for the olfactory marker protein. Our findings show that cells dissociated from the developing and adult olfactory organs when transplanted into the rat fetal brain can either completely change their fate and differentiate according to their final position or generate an olfactory epithelium if they reaggregate into large clusters.