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      Segregation of brain and organizer precursors is differentially regulated by Nodal signaling at blastula stage

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          ABSTRACT

          The blastula Chordin- and Noggin-expressing (BCNE) center comprises animal-dorsal and marginal-dorsal cells of the amphibian blastula and contains the precursors of the brain and the gastrula organizer. Previous findings suggested that the BCNE behaves as a homogeneous cell population that only depends on nuclear β-catenin activity but does not require Nodal and later segregates into its descendants during gastrulation. In contrast to previous findings, in this work, we show that the BCNE does not behave as a homogeneous cell population in response to Nodal antagonists. In fact, we found that chordin.1 expression in a marginal subpopulation of notochordal precursors indeed requires Nodal input. We also establish that an animal BCNE subpopulation of cells that express both, chordin.1 and sox2 (a marker of pluripotent neuroectodermal cells), and gives rise to most of the brain, persisted at blastula stage after blocking Nodal. Therefore, Nodal signaling is required to define a population of chordin.1+ cells and to restrict the recruitment of brain precursors within the BCNE as early as at blastula stage. We discuss our findings in Xenopus in comparison to other vertebrate models, uncovering similitudes in early brain induction and delimitation through Nodal signaling.

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          Summary: Nodal signaling is involved in the delimitation of the blastula cell populations that give rise to the brain and axial mesoderm in Xenopus.

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          Nodal signaling: developmental roles and regulation.

          Nodal-related ligands of the transforming growth factor-beta (TGFbeta) superfamily play central roles in patterning the early embryo during the induction of mesoderm and endoderm and the specification of left-right asymmetry. Additional roles for this pathway in the maintenance of embryonic stem cell pluripotency and in carcinogenesis have been uncovered more recently. Consistent with its crucial developmental functions, Nodal signaling is tightly regulated by diverse mechanisms including the control of ligand processing, utilization of co-receptors, expression of soluble antagonists, as well as positive- and negative-feedback activities.
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            Mouse gastrulation: the formation of a mammalian body plan.

            The process of gastrulation is a pivotal step in the formation of the vertebrate body plan. The primary function of gastrulation is the correct placement of precursor tissues for subsequent morphogenesis. There is now mounting evidence that the body plan is established through inductive interactions between germ layer tissues and by the global patterning activity emanating from embryonic organizers. An increasing number of mouse mutants have been described that have gastrulation defects, providing important insights into the molecular mechanisms that regulate this complex process. In this review, we explore the mouse embryo before and during gastrulation, highlighting its similarities with other vertebrate embryos and its unique characteristics.
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              Xenopus chordin: a novel dorsalizing factor activated by organizer-specific homeobox genes.

              Y Sasai (1994)
              A Xenopus gene whose expression can be activated by the organizer-specific homeobox genes goosecoid and Xnot2 was isolated by differential screening. The chordin gene encodes a novel protein of 941 amino acids that has a signal sequence and four Cys-rich domains. The expression of chordin starts in Spemann's organizer subsequent to that of goosecoid, and its induction by activin requires de novo protein synthesis. Microinjection of chordin mRNA induces twinned axes and can completely rescue axial development in ventralized embryos. This molecule is a potent dorsalizing factor that is expressed at the right time and in the right place to regulate cell-cell interactions in the organizing centers of head, trunk, and tail development.
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                Author and article information

                Journal
                Biol Open
                Biol Open
                BIO
                biolopen
                Biology Open
                The Company of Biologists Ltd
                2046-6390
                15 February 2021
                25 February 2021
                25 February 2021
                : 10
                : 2
                : bio051797
                Affiliations
                [1 ]Universidad de Buenos Aires. Facultad de Medicina, Departamento de Biología Celular e Histología / 1° U.A. Departamento de Histología, Embriología, Biología Celular y Genética, Laboratorio de Embriología Molecular “Prof. Dr. Andrés E. Carrasco”, Buenos Aires 1121, Argentina
                [2 ]CONICET - Universidad de Buenos Aires. Instituto de Biología Celular y Neurociencia “Prof. E. De Robertis” (IBCN) , Universidad de Buenos Aires, Buenos Aires 1121, Argentina
                [3 ]Instituto de Investigaciones en Ingeniería Genética y Biología Molecular (INGEBI) “Dr. Héctor N. Torres”, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) , Buenos Aires C1428, Argentina
                [4 ]Departamento de Fisiología, Biología Molecular y Celular, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires , Buenos Aires 1428, Argentina
                Author notes
                Author information
                http://orcid.org/0000-0002-8052-8344
                http://orcid.org/0000-0001-5558-0717
                http://orcid.org/0000-0002-0685-8601
                http://orcid.org/0000-0002-7500-7771
                http://orcid.org/0000-0001-6602-2243
                http://orcid.org/0000-0002-3760-7549
                Article
                BIO051797
                10.1242/bio.051797
                7928228
                33563608
                b9225281-919b-4fd8-9f13-ed53a671f34d
                © 2021. Published by The Company of Biologists Ltd

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.

                History
                : 3 March 2020
                : 29 January 2021
                Funding
                Funded by: Agencia Nacional de Promoción Científica y Tecnológica, http://dx.doi.org/10.13039/501100003074;
                Award ID: PICT 2011-1559, PICT 2014-2020
                Funded by: Consejo Nacional de Investigaciones Científicas y Técnicas, http://dx.doi.org/10.13039/501100002923;
                Award ID: PIP 2012-0508, PIP 2015-0577
                Categories
                Research Article

                Life sciences
                bcne center,nodal,chordin,gastrula organizer,brain,vertebrates
                Life sciences
                bcne center, nodal, chordin, gastrula organizer, brain, vertebrates

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