FGF2 plays a key role in embryonic cerebrospinal fluid trophic properties over chick embryo neuroepithelial stem cells

Abstract

During early stages of brain development, neuroepithelial stem cells undergo intense proliferation as neurogenesis begins. Fibroblast growth factor 2 (FGF2) has been involved in the regulation of these processes, and although it has been suggested that they work in an autocrine-paracrine mode, there is no general agreement on this because the behavior of neuroepithelial cells is not self-sufficient in explants cultured in vitro. In this work, we show that during early stages of development in chick embryos there is another source of FGF2, besides that of the neuroepithelium, which affects the brain primordium, since the cerebrospinal fluid (E-CSF) contains several isoforms of this factor. We also demonstrate, both in vitro and in vivo, that the FGF2 from the E-CSF has an effect on the regulation of neuroepithelial cell behavior, including cell proliferation and neurogenesis. In order to clarify putative sources of FGF2 in embryonic tissues, we detected by in situ hybridization high levels of mRNA expression in notochord, mesonephros and hepatic primordia, and low levels in brain neuroectoderm, corroborated by semiquantitative PCR analysis. Furthermore, we show that the notochord segregates several FGF2 isoforms which modify the behavior of the neuroepithelial cells in vitro. In addition, we show that the FGF2 ligand is present in the embryonic serum; and, by means of labeled FGF2, we prove that this factor passes via the neuroepithelium from the embryonic serum to the E-CSF in vivo. Considering all these results, we propose that, in chick embryos, the behavior of brain neuroepithelial stem cells at the earliest stages of development is influenced by the action of the FGF2 contained within the E-CSF which could have an extraneural origin, thus suggesting a new and complementary way of regulating brain development.

Expansion, folding, and abnormal lamination of the chick optic tectum after intraventricular injections of FGF2

“…Specifically, intraventricular injections of FGF2 in embryonic rats and mice increases neocortical neuron numbers (13,29), as one would expect if FGF2 prolongs precursor proliferation. Several studies suggest that proliferation rate and neuronal migration are relatively unaffected by FGF2 manipulations in vivo (13,(29)(30)(31), although in vitro studies have reported more complex effects (32).…”

Molecular anatomy and functions of the choroidal blood-cerebrospinal fluid barrier in health and disease

“…Decreasing hydrostatic pressure results in smaller brain ventricles, and smaller and disorganized neural tissue [63]. Factors within the embryonic CSF, including sonic hedgehog and choroid plexus-derived insulin-like growth factor 2, promote the proliferation of neural progenitors [59,78,90,170]. The CSF effect is optimal when age-matched CSF and tissue are combined, highlighting the dynamic nature of both the choroid plexus/CSF axis and of the intrinsic state of the responding cells [18,78].…”

A Comparative Proteomic Analysis of Human and Rat Embryonic Cerebrospinal Fluid

“…Gato et al and Martin et al have studied the role of chick e-CSF in regulating survival, proliferation, and neurogenesis of neuroepithelial cells, and identified FGF-2 in the chick CSF as a vital trophic factor. 15,16 Intriguingly, in mutant animals, CSF factors that may inhibit proliferation have been suggested. In studies of the hydrocephalic Texas (H-Tx) rat, it has been found that cell proliferation in the ventricular zone decreases, and although cell migration still occurs, there is a decrease in the number of migrating cells.…”