Cerebrospinal fluid control of neurogenesis induced by retinoic acid during early brain development

Abstract

Embryonic‐cerebrospinal fluid (E‐CSF) plays crucial roles in early brain development including the control of neurogenesis. Although FGF2 and lipoproteins present in the E‐CSF have previously been shown to be involved in neurogenesis, the main factor triggering this process remains unknown. E‐CSF contains all‐trans‐retinol and retinol‐binding protein involved in the synthesis of retinoic acid (RA), a neurogenesis inducer. In early chick embryo brain, only the mesencephalic‐rombencephalic isthmus (IsO) is able to synthesize RA. Here we show that in chick embryo brain development: (1) E‐CSF helps to control RA synthesis in the IsO by means of the RBP and all‐trans‐retinol it contains; (2) E‐CSF has retinoic acid activity, which suggests it may act as a diffusion pathway for RA; and (3) the influence of E‐CSF on embryonic brain neurogenesis is to a large extent due to its involvement in RA synthesis. These data help to understand neurogenesis from neural progenitor cells. Developmental Dynamics 240:1650–1659, 2011. © 2011 Wiley‐Liss, Inc.

Embryonic Cerebrospinal Fluid Activates Neurogenesis of Neural Precursors within the Subventricular Zone of the Adult Mouse Brain

“…Embryonic CSF has been demonstrated to be a key component of the embryonic brain stem cells niche, promoting survival, replication and neurogenesis in neuroepithelial precursors Alonso et al, 2011]. The embryonic CSF composition is complex [Gato et al, 2004;Parada et al, 2005;2006] and some of its components such as FGF2, IGFI and retinol-binding-protein, have been shown to be involved in mitogenic and neurogenic activity [Martín et al, 2006;Miyan et al, 2006;Alonso et al, 2011;Zappaterra and Lehtinen, 2012]. CSF also undergoes an ontogenic evolution and the changes in its composition and biological properties could explain the changes in stem cells niche activity.…”

Manual Drainage of the Zebrafish Embryonic Brain Ventricles

“…Identification of different proteins during this time will enable further investigation into the function of the CSF and its potential role during brain development. In amniotes, some factors identified in eCSF (IGF2, FGF2, retinoic acid, and apolipoproteins) have a demonstrated role in neuroepithelial cell survival, proliferation and neurogenesis 13,17,20,23,27,28 . However, there appear to be hundreds of uncharacterized proteins in the eCSF, which was obtained after choroid plexus formation, later than the time-points demonstrated here.…”

“…eCSF contains about three times more protein than adult CSF, suggesting that it may have an important role during development 8,9 . Studies in chick and mouse demonstrate that secreted factors in the eCSF, fluid pressure, or a combination of these, are important for neurogenesis, gene expression, cell proliferation, and cell survival in the neuroepithelium [10][11][12][13][14][15][16][17][18][19][20] . Proteomic analyses of human, rat, mouse, and chick eCSF have identified many proteins that may be necessary for CSF function.…”

Fetal Cerebrospinal Fluid Promotes Proliferation and Neural Differentiation of Stromal Mesenchymal Stem Cells Derived from Bone Marrow

“…These will eventually generate all the neurons and glial cells of the cerebral cortex together with the median and lateral eminence that provide post-natal neurogenesis and cortical interneurons (reviewed in (1,2). The neural tube and cephalic vesicles are filled with embryonic cerebrospinal fluid (E-CSF) which plays important roles in neural development at both embryonic and fetal stages, regulating the survival, proliferation, and neural differentiation of the neuroepithelial progenitor cells (3)(4)(5).At the start of the major phase of cortical development, high volume CSF is secreted by the ventricular choroid plexus (6). The generation of neurons and glia from proliferating neural progenitor/stem cells is a complex process (7)(8)(9).…”

“…Several evidence suggest that the E-CSF contains diffusible factors such as transforming growth factor-s (TGF-s), nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), insulinlike growth factor (IGF) and hepatocyte growth factor (HGF), basic fibroblastic growth factor (b-FGF) that regulating the survival, proliferation, and differentiation of primary cortical progenitor cells and neuroepithelium (7,12). In chick embryos at early stages of CNS development, E-CSF contains FGF2, that this FGF2 is involved in regulating the behavior of neuroectodermal cells, including cell proliferation and neurogenesis (3). NGF, BDNF, NT-3 and NT-4 are involved in many more aspects of neural development and function (11).…”