Neural differentiation without organizer

Barth, L. G.

doi:10.1002/jez.1400870303

Cited by 96 publications

(23 citation statements)

References 6 publications

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“…Gradually, the search for the Spemann organizer neural inducer became a funeral march for the field (reviewed by Holtfreter & Hamburger 1955). Eventually it was realized that neuralization of axolotl ectoderm could be obtained in the complete absence of any inducer simply by culturing animal caps in an inadequate saline solution (Barth 1941). This effect could be mimicked in other amphibians by partial cell dissociation with citrate, oxalate, or low pH treatments that received the unfortunate name of "sublethal cytolysis" (Holtfreter & Hamburger 1955).…”

Section: The Neural Induction Default Modelmentioning

confidence: 99%

DORSAL-VENTRAL PATTERNING AND NEURAL INDUCTION IN XENOPUS EMBRYOS

Robertis

Kuroda

2004

Annu. Rev. Cell Dev. Biol.

632

586

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We review the current status of research in dorsal-ventral (D-V) patterning in vertebrates. Emphasis is placed on recent work on Xenopus, which provides a paradigm for vertebrate development based on a rich heritage of experimental embryology. D-V patterning starts much earlier than previously thought, under the influence of a dorsal nuclear β-Catenin signal. At mid-blastula two signaling centers are present on the dorsal side: The prospective neuroectoderm expresses bone morphogenetic protein (BMP) antagonists, and the future dorsal endoderm secretes Nodal-related mesoderminducing factors. When dorsal mesoderm is formed at gastrula, a cocktail of growth factor antagonists is secreted by the Spemann organizer and further patterns the embryo. A ventral gastrula signaling center opposes the actions of the dorsal organizer, and another set of secreted antagonists is produced ventrally under the control of BMP4. The early dorsal β-Catenin signal inhibits BMP expression at the transcriptional level and promotes expression of secreted BMP antagonists in the prospective central nervous system (CNS). In the absence of mesoderm, expression of Chordin and Noggin in ectoderm is required for anterior CNS formation. FGF (fibroblast growth factor) and IGF (insulinlike growth factor) signals are also potent neural inducers. Neural induction by anti-BMPs such as Chordin requires mitogen-activated protein kinase (MAPK) activation mediated by FGF and IGF. These multiple signals can be integrated at the level of Smad1. Phosphorylation by BMP receptor stimulates Smad1 transcriptional activity, whereas phosphorylation by MAPK has the opposite effect. Neural tissue is formed only at very low levels of activity of BMP-transducing Smads, which require the combination of both low BMP levels and high MAPK signals. Many of the molecular players that regulate D-V patterning via regulation of BMP signaling have been conserved between Drosophila and the vertebrates.

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Section: The Neural Induction Default Modelmentioning

confidence: 99%

DORSAL-VENTRAL PATTERNING AND NEURAL INDUCTION IN XENOPUS EMBRYOS

Robertis

Kuroda

2004

Annu. Rev. Cell Dev. Biol.

632

586

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“…Neural induction in amphibians requires secreted signals, in particular BMP antagonists, produced in the dorsal organizer region of the embryo (Spemann 1938;Harland 2000;De Robertis and Kuroda 2004). However, early work also showed that brain tissue could be obtained in the absence of the organizer, for example, by simply culturing newt ectodermal explants in sub-optimal saline solutions (Barth 1941;Holtfreter 1944). In Xenopus, neural differentiation without the organizer can be induced by dissociating ectodermal cells, which would otherwise give rise to epidermis, for 3 h or more ( Two disparate views dominate the neural induction field at present.…”

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confidence: 99%

“…However, early work also showed that brain tissue could be obtained in the absence of the organizer, for example, by simply culturing newt ectodermal explants in sub-optimal saline solutions (Barth 1941;Holtfreter 1944). In Xenopus, neural differentiation without the organizer can be induced by dissociating ectodermal cells, which would otherwise give rise to epidermis, for 3 h or more (Grunz and Tacke 1989;Sato and Sargent 1989).…”

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confidence: 99%

Default neural induction: neuralization of dissociated Xenopus cells is mediated by Ras/MAPK activation

Kuroda¹,

et al. 2005

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Xenopus embryonic ectodermal cells dissociated for three or more hours differentiate into neural tissue instead of adopting their normal epidermal fate. This default type of neural induction occurs in the absence of Spemann's organizer signals and is thought to be caused by the dilution of endogenous BMPs into the culture medium. Unexpectedly, we observed that BMP ligands continue to signal in dissociated cells. Instead, cell dissociation induces a sustained activation of the Ras/ MAPK pathway, which causes the phosphorylation of Smad1 at sites that inhibit the activity of this transcription factor. It is this activation of Ras/MAPK that is required for neuralization in dissociated ectoderm. Neural induction in amphibians requires secreted signals, in particular BMP antagonists, produced in the dorsal organizer region of the embryo (Spemann 1938;Harland 2000;De Robertis and Kuroda 2004). However, early work also showed that brain tissue could be obtained in the absence of the organizer, for example, by simply culturing newt ectodermal explants in sub-optimal saline solutions (Barth 1941;Holtfreter 1944). In Xenopus, neural differentiation without the organizer can be induced by dissociating ectodermal cells, which would otherwise give rise to epidermis, for 3 h or more ( Two disparate views dominate the neural induction field at present. Work in the chick embryo has stressed the importance of FGF signaling, whereas work in Xenopus has tended to emphasize the requirement for antiBMPs in neural induction (Harland 2000; Stern 2004). We have argued that these apparently conflicting observations can be reconciled through a molecular mechanism in which Ras/MAPK phosphorylation regulates the BMP transducers Smad1/5/8 (De Robertis and Kuroda 2004). It has been reported that both FGF and IGF can promote neural induction through the phosphorylation, via MAPK, of inhibitory sites located in the linker region of the Smad1 transcription factor (Pera et al. 2003). Linker phosphorylation of BMP-sensitive Smads by MAPK opposes the effect of C-terminal Smad phosphorylation by the BMP receptor serine-threonine protein kinase (Fig. 1A), causing inhibition of the nuclear function of Smad1 and promoting neural development (low BMP/Smad) at the expense of epidermal (high BMP/ Smad) fates (Massagué 2003).It is known that activation of ERK can be triggered by a large number of external stimuli, including cell stress (Wetzker and Böhmer 2003). In Xenopus embryos, the simple extirpation of ectodermal explants can activate ERK, causing this kinase to become diphosphorylated (dpERK) (LaBonne and Whitman 1997; Christen and Slack 1999). However, this ERK activation by microsurgery is transient, lasting <30 min. Transient ERK activation after animal cap dissection is without phenotypic effect, and the explants go on to differentiate according to their normal epidermal fate. Since BMP and MAPK signaling are integrated during neural induction, we decided to investigate whether cell dissociation in conditions that cause neural differentiation mi...

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“…It was first discovered by Barth [1941], and later confirmed by Holtfreter [1944Holtfreter [ , 1945 that, in contrast to other amphibian species, explants made from embryos of Ambystoma punctatum very easily may be pro voked to undergo autoneuralization. The ex perimental results reported above show that the process of autoneuralization in A. mexicanum is markedly stage-specific, being ab sent before gastrulation has begun.…”

Section: Discussionmentioning

confidence: 99%

Autoneuralization in the Amphibian Ectoderm -A Species-Specific and Stage-Specific Phenomenon

Nakatsuji

Løvtrup³

1987

Pathobiology

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Ectoderm from Ambystoma is especially prone to undergo ‘autoneuralization’. This assertion has led to the maxim that ectoderm from this species is unsuitable for studying cell differentiation. Here we report that the degree of neuralization in cultured explants is stage-dependent. Control explants from blastulae (stage 8-9) show no neuralization, while explants treated with LiCl (10 mM) give rise to neuralization in about 70% of the cases. This difference between control and experiment decreases during gastrulation, in late gastrulae (stage 12) it is more or less negligible. Ectoderm from Cynops pyrrhogaster reacts like that of Ambystoma when exposed to LiCl, but like Triturus ectoderm it is insensitive to cyclic nucleotides.

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Neural differentiation without organizer

Cited by 96 publications

References 6 publications

DORSAL-VENTRAL PATTERNING AND NEURAL INDUCTION IN XENOPUS EMBRYOS

DORSAL-VENTRAL PATTERNING AND NEURAL INDUCTION IN XENOPUS EMBRYOS

Default neural induction: neuralization of dissociated Xenopus cells is mediated by Ras/MAPK activation

Autoneuralization in the Amphibian Ectoderm -A Species-Specific and Stage-Specific Phenomenon

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