Journal
DEVELOPMENTAL BIOLOGY
Volume 307, Issue 2, Pages 282-289Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ydbio.2007.04.049
Keywords
Ambystonia maculatum; Xenopus; Ras; MAPK; ERK; BMP; FGF; brain differentiation; Smad1; embryonic induction
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Funding
- NICHD NIH HHS [R01 HD021502, R37 HD021502-20, HD21502-20, R37 HD021502] Funding Source: Medline
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Research on the mechanisms of embryonic induction had a great setback in the 1940s when Barth discovered and Holtfreter confirmed that ectoderm of Ambystoma maculatum salamander embryos could form brain tissue when cultured in a simple saline solution. We have revisited this classical experiment and found that when cultured animal cap ectoderm attaches to a glass substratum, it can self-organize to form complex organs such as brain vesicles, eyes, lens and olfactory placodes. Only anterior neural organs were generated. Under these culture conditions ERK became diphosphorylated, indicating a sustained activation of the Ras/MAPK pathway. Using sand particles as an example of a heterologous neural inducer similar results were obtained. Addition of U0126, a specific antagonist of MEK, the enzyme that phosphorylates ERK/MAPK, inhibited neural differentiation. The closely related control compound U0124 had no effect. We conclude that neural induction in the absence of organizer in A. maculatum requires Ras/MAPK-activation. These findings provide a molecular explanation for the activity of heterologous neural inducers that dominated thinking in amphibian experimental embryology for many decades. (c) 2007 Elsevier Inc. All rights reserved.
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