Characterization of the human nestin gene reveals a close evolutionary relationship to neurofilaments

Abstract

Multipotential stem cells in the neural tube give rise to the different neuronal cell types found in the brain. Abrupt changes in intermediate filament gene expression accompany this transition out of the precursor state: transcription of the intermediate filament nestin is replaced by that of the neurofilaments. In order to identify human neural precursor cells, and to learn more about the evolution of the intermediate filaments expressed in the central nervous system, we have isolated the human nestin gene. Despite considerable divergence between the human and rat nestin genes, in particular in the repetitive parts of the carboxyterminal region, the positions of the introns are perfectly conserved. Two of the three intron positions are also shared by the neurofilaments, but not by other classes of inter-mediate filaments. This implies that nestin and the neu-rofilaments had a common ancestor after branching off from the other classes of intermediate filaments, and that nestin separated from the neurofilament branch before the different neurofilament genes diverged. The characterization of human nestin also facilitates the identification of human multipotential neural precursor cells. This will be of importance for central nervous system (CNS) tumor diagnosis and transplant-based clinical approaches to human neurodegenerative diseases.