Molecular milestones that signal axonal maturation and the commitment of human spinal cord precursor cells to the neuronal or glial phenotype in development

Abstract

Insights into the programmatic induction of neuronal and glial genes during human embryogenesis have depended largely on extrapolations of data derived from experimental mammals. However, the assumptions upon which these extrapolations are based have not been rigorously tested. Indeed, practically no information is available even on the human counterparts of the relatively small subset of well-characterized, developmentally regulated neuron and glial specific genes of the mammalian CNS. Thus, the developmental programs upon which human neural embryogenesis are based remain largely undeciphered. We have addressed this problem in immunohistochemical studies conducted on 22 human fetal spinal cords with gestational ages (GAs) that ranged from 6 to 40 weeks by using monoclonal antibodies to several classes of neuron or glial specific polypeptides. These polypeptides included: representatives of four different types (Types I-IV) of intermediate filament proteins, i.e., vimentin filament protein (VFP), glial fibrillary acidic protein (GFAP), different phospho-isoforms of the high (NF-H), middle (NF-M), and low (NF-L) molecular weight (Mr) neurofilament (NF) subunits, both acidic and basic cytokeratin (CK) proteins; three different microtubule associated proteins (MAPs), i.e., MAP2, MAP5, and tau; two different synaptic or coated vesicle proteins, i.e., synaptophysin (SYP) and clathrin light chain B (LCb); an oligodendroglial specific protein, i.e., myelin basic protein (MBP); and a receptor for a CNS trophic factor, i.e., the nerve growth factor receptor (NGFR).(ABSTRACT TRUNCATED AT 400 WORDS)