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In this review, favouring the neural default model, the authors summarise recent results obtained using mouse embryonic stem cells. Some of these experiments show differential effects of Bmp signaling, that depend on the culturing conditions. Although neural differentiation is always blocked by Bmps, they can promote either the maintenance of stem cells (when Fgf2 is present) or epidermal differentiation.
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This paper reports the identification in a two-hybrid screen of Frodo, a new Xenopus protein that interacts with Dsh during canonical Wnt signaling. The authors demonstrate that Frodo synergizes with Dsh in secondary axis induction. Interestingly, Frodo appears to be strongly expressed in the anterior neural plate and eye field, and is necessary for the development of these territories.
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Gloy J., Hikasa H., Sokol S. Frodo interacts with Dishevelled to transduce Wnt signals. Nat. Cell. Biol. 4:2002;351-357 This paper reports the identification in a two-hybrid screen of Frodo, a new Xenopus protein that interacts with Dsh during canonical Wnt signaling. The authors demonstrate that Frodo synergizes with Dsh in secondary axis induction. Interestingly, Frodo appears to be strongly expressed in the anterior neural plate and eye field, and is necessary for the development of these territories.
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In a continuation of the study by Wilson et al. [23], the authors show that Wnt signalling modulates the responses of cells to Fgf and Bmp signaling in chick explants. In central epiblast explants, neural fates can only be induced by Fgf signaling when Wnt signaling is inhibited, whereas lateral epiblast explants require Fgf signaling in the absence of Bmp and Wnt signaling.
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Wilson S.I., Rydström A., Trimborn T., Willert K., Nusse R., Jessell T.M., Edlund T. The status of Wnt signaling regulates neural and epidermal fates in the chick embryo. Nature. 411:2001;325-330 In a continuation of the study by Wilson et al. [23], the authors show that Wnt signalling modulates the responses of cells to Fgf and Bmp signaling in chick explants. In central epiblast explants, neural fates can only be induced by Fgf signaling when Wnt signaling is inhibited, whereas lateral epiblast explants require Fgf signaling in the absence of Bmp and Wnt signaling.
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In this paper, gain- and loss-of-function data are presented that suggest that Insulin-like growth factor signals are necessary and sufficient for the induction of anterior neural development. Three different Insulin-like growth factors IGF1-3, IGF binding protein 5 (IGFBP5), and an IGF receptor are present on the dorsal side of Xenopus gastrula embryos. Application of IGF or IGFBP5 mRNA results in the formation of ectopic eyes and brain structures in embryos, and in the anterior expression of neural marker genes in animal cap explants. Application of mRNA encoding a dominant negative IGF receptor inhibits neural induction by Bmp antagonists such as Chordin. The latter finding suggests that IGFs are positive neural inducers acting in parallel to, rather than via, a Bmp blockage.
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The recent findings of the McKay laboratory are reviewed in the light of the differential roles of BMP, Fgf, Wnt, Shh, and Notch signaling during different phases of embryonic neural development and neural stem-cell biology. An induction-termination mechanism is proposed, according to which BMPs can coordinate positional identity with self-renewal/proliferation and mitotic arrest/terminal differentiation in the neural tube of mouse embryos. In the induction phase, BMP signaling, mediated by the receptor BMPR1a, instructs neural precursor cells to proliferate and to acquire dorsal identities. In parallel, BMPR1b expression is induced. When levels of BMPR1b exceed those of BMPR1a, cells respond to BMPs with mitotic arrest (termination phase). This leads to apoptosis or differentiation of neural precursor cells, depending or the presence of absence of additional competence factors.
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Panchision D.M., McKay R.D.G. The control of neural stem cells by morphogenetic signals. Curr. Opin. Genet. Dev. 12:2002;478-487 The recent findings of the McKay laboratory are reviewed in the light of the differential roles of BMP, Fgf, Wnt, Shh, and Notch signaling during different phases of embryonic neural development and neural stem-cell biology. An induction-termination mechanism is proposed, according to which BMPs can coordinate positional identity with self-renewal/proliferation and mitotic arrest/terminal differentiation in the neural tube of mouse embryos. In the induction phase, BMP signaling, mediated by the receptor BMPR1a, instructs neural precursor cells to proliferate and to acquire dorsal identities. In parallel, BMPR1b expression is induced. When levels of BMPR1b exceed those of BMPR1a, cells respond to BMPs with mitotic arrest (termination phase). This leads to apoptosis or differentiation of neural precursor cells, depending or the presence of absence of additional competence factors.
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Tiarin is a novel secreted protein of the olfactomedin-related family. Like BMPs, this protein is generated in the nonneural ectoderm adjacent to the anterior neural ectoderm of gastrulating Xenopus embryos. Forced expression of either Tiarin or BMPs leads to a dorsalization of the neural tube. However, unlike Bmps, Tiarian does not display any anti-neuralizing activity, suggesting that it might cooperate with Bmps during the dorsoventral patterning of the neural tube, but not during inhibition of neural induction.
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Tsuda H., Sasai N., Masuo-Takasaki M., Sakuragi M., Murakami Y., Sasai Y. Dorsalization of the neural tube by Xenopus Tiarin, a novel patterning factor secreted by the flanking nonneural head ectoderm. Neuron. 33:2002;518-528 Tiarin is a novel secreted protein of the olfactomedin-related family. Like BMPs, this protein is generated in the nonneural ectoderm adjacent to the anterior neural ectoderm of gastrulating Xenopus embryos. Forced expression of either Tiarin or BMPs leads to a dorsalization of the neural tube. However, unlike Bmps, Tiarian does not display any anti-neuralizing activity, suggesting that it might cooperate with Bmps during the dorsoventral patterning of the neural tube, but not during inhibition of neural induction.
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In this exciting paper, the authors demonstrate that in ovo electroporation of Wnt1 and Wnt3a in chick spinal cords promotes cell proliferation via the β-catenin/TCF pathway and the induction of cyclin D1 and D2. This dorsal-to-ventral gradient of mitogenic Wnt signaling is inversely correlated to the ventral-to-dorsal gradient of neural differentiation. Computer modeling suggests that canonical Wnt signaling from the dorsal midline of the neural tube constitutes a self-regulating stem-cell maintenance system, which promotes cell cycle progression and blocks neurogenesis in a graded fashion.
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This interesting article suggests that factors triggering early cell cycle exit and factors controlling the acquisition of early neuronal cell fates functionally cooperate to achieve the distinct neuronal differentiation pattern of the Xenopus retina.
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Ohnuma S., Hopper S., Wang K.C., Philpott A., Harris W.A. Co-ordinating retinal histogenesis: early cell cycle exit enhances early cell fate determination in the Xenopus retina. Development. 129:2002;2435-2446 This interesting article suggests that factors triggering early cell cycle exit and factors controlling the acquisition of early neuronal cell fates functionally cooperate to achieve the distinct neuronal differentiation pattern of the Xenopus retina.
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(2002)
Development
, vol.129
, pp. 2435-2446
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Ohnuma, S.1
Hopper, S.2
Wang, K.C.3
Philpott, A.4
Harris, W.A.5
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88
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0034965648
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FGF receptor signalling is required to maintain neural progenitors during Henson's node progression
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Using co-electroporation of a lineage marker and a dominant negative Fgf receptor in chick embryos, the authors demonstrate that Fgf signaling is required for the development of the posterior nervous tissue. Specifically Fgf signaling maintains a proliferative stem-cell zone of neural progenitors near Henson's node. This suggests that Fgf signaling, despite its role in promoting early steps of neural specification, is later involved in maintaining an immature neural state, blocking the final steps of neuronal differentiation.
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Mathis L., Kulesa P.M., Fraser S.E. FGF receptor signalling is required to maintain neural progenitors during Henson's node progression. Nat. Cell. Biol. 3:2001;559-566 Using co-electroporation of a lineage marker and a dominant negative Fgf receptor in chick embryos, the authors demonstrate that Fgf signaling is required for the development of the posterior nervous tissue. Specifically Fgf signaling maintains a proliferative stem-cell zone of neural progenitors near Henson's node. This suggests that Fgf signaling, despite its role in promoting early steps of neural specification, is later involved in maintaining an immature neural state, blocking the final steps of neuronal differentiation.
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(2001)
Nat. Cell. Biol.
, vol.3
, pp. 559-566
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Mathis, L.1
Kulesa, P.M.2
Fraser, S.E.3
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89
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0035499887
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The development of neural stem cells
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Temple S. The development of neural stem cells. Nature. 414:2002;112-117.
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(2002)
Nature
, vol.414
, pp. 112-117
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Temple, S.1
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