FGF2/EGF contributes to brain neuroepithelial precursor proliferation and neurogenesis in rat embryos: the involvement of embryonic cerebrospinal fluid.

BACKGROUND: At the earliest stages of brain development, the neuroepithelium works as an interdependent functional entity together with cerebrospinal fluid, which plays a key regulatory role in neuroepithelial cell survival, replication and neurogenesis; however, the underlying mechanism remains unknown in mammals. RESULTS: We show the presence of fibroblast growth factor 2 (FGF2) and epidermal growth factor (EGF), in 13.5-day rat embryo cerebrospinal fluid (eCSF). Immunohistochemical detection of FGF2 expression localized this factor inside neuroepithelial precursors close to the neuroepithelial-CSF interface, suggesting that FGF2 from eCSF could originate in the neuroepithelium by apical secretion. The colocalization of FGFR1 and FGF2 in some neuroepithelial cells close to the ventricular surface suggests they are target cells for eCSF FGF2. Brain neuroepithelium EGF expression was negative. By using a neuroepithelial organotypic culture, we demonstrate that FGF2 and EGF from eCSF plays a specific role in triggering the self-renewal and are involved in neurogenetic induction of mesencephalic neuroepithelial precursor cells during rat development. CONCLUSIONS: We propose eCSF as an intercommunication medium for neuroepithelial precursor behavior control during early rat brain development, and the neuroepithelial regulation of FGF2 and EGF presence in eCSF, as a regulative mechanism controlling precursor proliferation and neurogenesis.

Embryonic cerebrospinal fluid activates neurogenesis of neural precursors within the subventricular zone of the adult mouse brain.

INTRODUCTION: There is a nondeveloped neurogenic potential in the adult mammalian brain, which could be the basis for neuroregenerative strategies. Many research efforts have been made to understand the control mechanisms which regulate the transition from a neural precursor to a neuron in the adult brain. Embryonic cerebrospinal fluid (CSF) is a complex fluid which has been shown to play a key role in neural precursor behavior during development, working as a powerful neurogenic inductor. We tested if the neurogenic properties of embryonic CSF are able to increase the neurogenic activity of neuronal precursors from the subventricular zone (SVZ) in the brains of adult mice. RESULTS: Our results show that mouse embryonic CSF significantly increases the neurogenic activity in precursor cells from adult brain SVZ. This intense neurogenic effect was specific for embryonic CSF and was not induced by adult CSF. CONCLUSIONS: Embryonic CSF is a powerful neurogenesis inductor in homologous neuronal precursors in the adult brain. This property of embryonic CSF could be a useful tool in neuroregeneration strategies.