Article

HB-GAM inhibits proliferation and enhances differentiation of neural stem cells

Neuroscience Center, Department of Biosciences and Institute of Biotechnology, University of Helsinki, Helsinki 00014, Finland.
Molecular and Cellular Neuroscience (Impact Factor: 3.73). 06/2004; 26(1):75-88. DOI: 10.1016/j.mcn.2004.01.018
Source: PubMed

ABSTRACT Proliferation of neural stem cells in the embryonic cerebral cortex is regulated by many growth factors and their receptors. Among the key molecules stimulating stem cell proliferation are FGF-2 and the FGF receptor-1. This ligand-receptor system is highly dependent on the surrounding heparan sulfates. We have found that heparin-binding growth-associated molecule (HB-GAM, also designated as pleiotrophin) regulates neural stem cell proliferation in vivo and in vitro. Deficiency of HB-GAM results in a pronounced, up to 50% increase in neuronal density in the adult mouse cerebral cortex. This phenotype arises during cortical neurogenesis, when HB-GAM knockout embryos display an enhanced proliferation rate as compared to wild-type embryos. Further, our in vitro studies show that exogenously added HB-GAM inhibits formation and growth of FGF-2, but not EGF, stimulated neurospheres, restricts the number of nestin-positive neural stem cells, and inhibits FGF receptor phosphorylation. We propose that HB-GAM functions as an endogenous inhibitor of FGF-2 in stem cell proliferation in the developing cortex.

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    • "Approximately 82% of the variance in EC thickness was accounted for by neuronal area and inter-neuronal distance in layers IV and V, suggesting that different but proportional neuronal area and inter-neuronal distance irregularities might exist in other cortical layers or that abnormalities exist exclusively in layers IV and V. Comparable overall EC thickness between KOs and WTs suggests the latter and indicates the presence of subtle, layer-specific neuronal irregularities not detectable via gross measures of overall cortical morphology. Collectively, these data are consistent with the observation of grossly normal brain size [24] but increased neuronal density in the frontal and parietal cortices of PTN KOs [9]. "
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