Induction of Perlecan Expression and Neural Cell Proliferation by FGF-2 in the Developing Cerebral Cortex: An In Vivo Study

Abstract

Fibroblast growth factor has been implicated in cerebral cortical cell proliferation, migration, survival and differentiation. In the nervous system, proteoglycans (PGs) modulate growth factor activities and cell proliferation. Perlecan is a large PG and is expressed during the prenatal stages of brain development. Perlecan can promote fibroblast growth factor-2 (FGF-2) activity. In this study the effects of FGF-2 on neurogenesis and perlecan expression in the cerebral cortex have been studied. FGF-2 and anti-FGF-2 antibody were administered to 1-day-old mouse pups through the cisterna magna. Two days after injection, the pups were harvested and brains were removed for further analysis. We used western blotting and immunohistochemistry in order to analyze perlecan expression and neurogenesis in the cerebral cortex. We showed that the thickness of cerebral cortex, the number of cells produced in the cerebral cortex and perlecan expression are increased in response to injection of FGF-2 and decreased in response to infusion of anti-FGF-2 antibody as compared to controls. In conclusion, the results from this study suggest that FGF-2 increases neural cell production and perlecan expression in the developing cerebral cortex. It is also concluded that FGF-2 is an important factor in the cerebral cortical development, stimulating neuronal precursor proliferation.

Heparan sulfate proteoglycans: a sugar code for vertebrate development?

“…Specific core proteins also play major roles in neurogenesis. The expression of perlecan is increased in response to Fgf2 ( Mashayekhi et al, 2011 ), and mice lacking perlecan (Hspg2 – Mouse Genome Informatics) show reduced cell proliferation leading to microcephaly with thinner cerebral walls ( Girós et al, 2007 ). Perlecan is also required for the maintenance of NSCs, as both the size of the NSC population and the extent of neurogenesis are strongly reduced in the SVZ of adult mice lacking perlecan ( Kerever et al, 2014 ).…”

A gradient of matrix-bound FGF-2 and perlecan is available to lens epithelial cells

“…This FGF-2 will likely be bound to perlecan in the lens capsule, which not only protects FGF-2 from degradation, but also regulates its availability to the lens epithelial cells ( Evans et al., 2002; Tumova and Bame, 1997 ). HSPGs are also established regulators of morphogen gradients ( Giraldez et al., 2002 ), but FGF-2 can also influence HSPG processing ( Sasisekharan et al., 1997; Tumova and Bame, 1997; Tumova et al., 1999 ) and can also increase HSPG synthesis ( Evans et al., 2002; Mashayekhi et al., 2011 ) as a feedback loop that could further regulate the levels of FGF-2. Such issues have yet to be investigated for the lens capsule.…”

Choroid plexus trophic factors in the developing and adult brain

“…In early CP development, FGF expression, particularly FGF2, modulates gene expression and activity, suggesting that FGF signaling maintains CP integrity and function (Greenwood et al, 2008). Secreted FGF2 has also been shown to have a role in the developing brain by regulating cell proliferation/neurogenesis and corticogenesis (Vaccarino et al, 1999;Mashayekhi et al, 2011).…”