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      The Multiple Roles of FGF Signaling in the Developing Spinal Cord

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          Abstract

          During vertebrate embryonic development, the spinal cord is formed by the neural derivatives of a neuromesodermal population that is specified at early stages of development and which develops in concert with the caudal regression of the primitive streak. Several processes related to spinal cord specification and maturation are coupled to this caudal extension including neurogenesis, ventral patterning and neural crest specification and all of them seem to be crucially regulated by Fibroblast Growth Factor (FGF) signaling, which is prominently active in the neuromesodermal region and transiently in its derivatives. Here we review the role of FGF signaling in those processes, trying to separate its different functions and highlighting the interactions with other signaling pathways. Finally, these early functions of FGF signaling in spinal cord development may underlay partly its ability to promote regeneration in the lesioned spinal cord as well as its action promoting specific fates in neural stem cell cultures that may be used for therapeutical purposes.

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          Most cited references161

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          The cell biology of neurogenesis.

          During the development of the mammalian central nervous system, neural stem cells and their derivative progenitor cells generate neurons by asymmetric and symmetric divisions. The proliferation versus differentiation of these cells and the type of division are closely linked to their epithelial characteristics, notably, their apical-basal polarity and cell-cycle length. Here, we discuss how these features change during development from neuroepithelial to radial glial cells, and how this transition affects cell fate and neurogenesis.
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            Differentiation of embryonic stem cells to clinically relevant populations: lessons from embryonic development.

            The potential to generate virtually any differentiated cell type from embryonic stem cells (ESCs) offers the possibility to establish new models of mammalian development and to create new sources of cells for regenerative medicine. To realize this potential, it is essential to be able to control ESC differentiation and to direct the development of these cells along specific pathways. Embryology has offered important insights into key pathways regulating ESC differentiation, resulting in advances in modeling gastrulation in culture and in the efficient induction of endoderm, mesoderm, and ectoderm and many of their downstream derivatives. This has led to the identification of new multipotential progenitors for the hematopoietic, neural, and cardiovascular lineages and to the development of protocols for the efficient generation of a broad spectrum of cell types including hematopoietic cells, cardiomyocytes, oligodendrocytes, dopamine neurons, and immature pancreatic beta cells. The next challenge will be to demonstrate the functional utility of these cells, both in vitro and in preclinical models of human disease.
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              In vitro differentiation of transplantable neural precursors from human embryonic stem cells.

              The remarkable developmental potential and replicative capacity of human embryonic stem (ES) cells promise an almost unlimited supply of specific cell types for transplantation therapies. Here we describe the in vitro differentiation, enrichment, and transplantation of neural precursor cells from human ES cells. Upon aggregation to embryoid bodies, differentiating ES cells formed large numbers of neural tube-like structures in the presence of fibroblast growth factor 2 (FGF-2). Neural precursors within these formations were isolated by selective enzymatic digestion and further purified on the basis of differential adhesion. Following withdrawal of FGF-2, they differentiated into neurons, astrocytes, and oligodendrocytes. After transplantation into the neonatal mouse brain, human ES cell-derived neural precursors were incorporated into a variety of brain regions, where they differentiated into both neurons and astrocytes. No teratoma formation was observed in the transplant recipients. These results depict human ES cells as a source of transplantable neural precursors for possible nervous system repair.
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                Author and article information

                Contributors
                Journal
                Front Cell Dev Biol
                Front Cell Dev Biol
                Front. Cell Dev. Biol.
                Frontiers in Cell and Developmental Biology
                Frontiers Media S.A.
                2296-634X
                02 June 2017
                2017
                : 5
                : 58
                Affiliations
                [1] 1Department of Cellular, Molecular and Developmental Neurobiology, Cajal Institute, Consejo Superior de Investigaciones Científicas Madrid, Spain
                [2] 2Champalimaud Research, Champalimaud Centre for the Unknown Lisbon, Portugal
                Author notes

                Edited by: Juan Jose Sanz-Ezquerro, Centro Nacional de Biotecnología, Spain

                Reviewed by: Cristina Pujades, Pompeu Fabra University, Spain; Gregg Duester, Sanford Burnham Prebys Medical Discovery Institute, United States; Benjamin Louis Martin, Stony Brook University, United States

                *Correspondence: Ruth Diez del Corral ruth.diezdelcorral@ 123456neuro.fchampalimaud.org

                This article was submitted to Signaling, a section of the journal Frontiers in Cell and Developmental Biology

                Article
                10.3389/fcell.2017.00058
                5454045
                28626748
                e0882b2c-4154-4a07-b623-dbfaf2a2ca03
                Copyright © 2017 Diez del Corral and Morales.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 17 February 2017
                : 11 May 2017
                Page count
                Figures: 4, Tables: 0, Equations: 0, References: 178, Pages: 18, Words: 16788
                Funding
                Funded by: Ministerio de Economía y Competitividad 10.13039/501100003329
                Award ID: BFU2014-57494-R
                Funded by: Champalimaud Foundation
                Categories
                Cell and Developmental Biology
                Review

                spinal cord,spinal cord injury,neuromesodermal progenitors,neural stem cells,patterning,neurogenesis,caudal extension,fgf

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