Segregation of human neural stem cells in the developing primate forebrain.

Many central nervous system regions at all stages of life contain neural stem cells (NSCs). We explored how these disparate NSC pools might emerge. A traceable clone of human NSCs was implanted intraventricularly to allow its integration into cerebral germinal zones of Old World monkey fetuses. The NSCs distributed into two subpopulations: One contributed to corticogenesis by migrating along radial glia to temporally appropriate layers of the cortical plate and differentiating into lamina-appropriate neurons or glia; the other remained undifferentiated and contributed to a secondary germinal zone (the subventricular zone) with occasional members interspersed throughout brain parenchyma. An early neurogenetic program allocates the progeny of NSCs either immediately for organogenesis or to undifferentiated pools for later use in the "postdevelopmental" brain.

Neural transplantation of hNT neurons for Huntington's disease.

Fetal striatal tissue transplants have been shown to restore motor deficits in rat and monkey models of Huntington's disease (HD). In the present study, using rats with unilateral striatal lesions, we compared fetal striatal tissue transplants to transplants of human NT (hNT) neurons. hNT neurons are terminally differentiated cells derived from the human NTera-2 cell line. In vitro, we have found that purified hNT neurons have a biochemical phenotype similar to that of human fetal striatal tissue. Both hNT neurons and fetal striatal tissue express mRNAs for glutamic acid decarboxylase, choline acetyltransferase, and the D1 and D2 dopamine receptors. Grafts of either hNT neurons or fetal striatal tissue into unilateral quinolinic acid-lesioned rat striatum improved methamphetamine-induced circling behavior. Sham controls showed no changes in methamphetamine-induced circling behavior. In the staircase test for skilled forelimb use, both transplant groups showed partial recovery in skilled use of the paw contralateral to the side of lesion, whereas the control animals showed continued deficits. These findings suggest that transplantation of hNT neurons may be an alternative to transplantation of fetal striatal tissue in the treatment of HD.

Avascular necrosis of bone in dyskeratosis congenita.

A case of dyskeratosis congenita, a rare X-linked disorder, is presented. The patient had the classic triad of cutaneous findings: reticulated hyperpigmentation, nail dystrophy, and leukoplakia. In addition, a previously unreported finding developed, avascular necrosis of bone without systemic steroid therapy. Recognition of this disorder is important because pancytopenia and malignancy develop in up to 50 percent of patients.