Abstract
One of the more intriguing subjects in neuroscience is how a precursor or stem cell is induced to differentiate into a neuron. Neurogenesis begins early in brain development and suddenly becomes a very intense process, which is related with the influence of Retinoic Acid. Here, using a biological test (F9-1.8 cells) in chick embryos, we show that “in vivo” embryonic cerebrospinal fluid regulates mesencephalic-rombencephalic Isthmic Retinoic Acid synthesis and this effect has a direct influence on mesencephalic neuroepithelial precursors, inducing a significant increase in neurogenesis. This effect is mediated by the Retinol Binding Protein present in the embryonic cerebrospinal fluid. The knowledge of embryonic neurogenetic stimulus could be useful in the control of adult brain neurogenesis.
Highlights
Embryonic Cerebrospinal Fluid (E-CSF) has been shown to play key functions in brain development at both embryonic and foetal stages, [1,2,3,4,5,6,7,8]
In live tissues, and in order to avoid the dispersion of these cells inside the brain cavity, we microinjected them deep in the cephalic mesenchyme in the dorsal region of the IsO, which has been described as the main location in the early chick embryonic brain that expresses Retinaldehyde Dehydrogenases (RALDHs) and which might produce Retinoic Acid (RA)
Here we show that ―in vivo‖ F9-1.8 cells microinjected close to but outside the neuroepithelilum are able to respond to RA secretion from the IsO cells, suggesting that, in vivo, the IsO cells produce an active form of Retinoic Acid which seems diffuse both peripherally and radially outside the IsO neuroepithelium, establishing an ―area of influence‖
Summary
Embryonic Cerebrospinal Fluid (E-CSF) has been shown to play key functions in brain development at both embryonic and foetal stages, [1,2,3,4,5,6,7,8]. Studies focusing on avian and mammal E-CSF proteomic composition reveal that this fluid includes a broad set of molecules, which might be responsible of their biological properties [12,13,14,15], and it has been suggested that there are specific molecules as FGF2 involved in specific cellular events, such neuroepithelial mitotic behavior [16] Another key molecule in development, namely Retinoic Acid (RA), has been described as a powerful neurogenic agent in both embryo and adult neural progenitor cells [17,18,19]. Using a similar experimental approach, we wish to ascertain if the same brain developmental mechanisms operate in live chick embryos
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