Fate of cloned embryonic neuroectodermal cells implanted into the adult, newborn and embryonic forebrain.

NE-4C, one-cell derived neuroectodermal stem cells expressing a reporter gene--green fluorescent protein (GFP) or heat-resistant alkaline phosphatase (PLAP)--or prelabeled with bromodeoxyuridine (BrdU) were implanted into the forebrain of adult, new-born and fetal mice and into the mid- and forebrain vesicles of early chick embryos. The fate of implanted cells in the mouse and chick hosts was followed up to 6 and 2 weeks, respectively. Neural differentiation was monitored by detecting the expression of neuron-specific markers and GFAP. NE-4C cells integrated into the early embryonic brain tissue and developed into morphologically differentiated neurons. The same cells produced expanding tumor-like aggregates in the newborn forebrain and were expelled from the adult forebrain parenchyma. In the adult brain, long-term survival and integration of stem cells were revealed only in neurogenic zones. The data suggest that noncommitted, proliferating neuroectodermal progenitors can integrate into the brain tissue at time and site of tissue genesis.