title: Neural induction in the absence of organizer in salamanders is mediated by MAPK.
abstract: 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.
authors.affiliation: Howard Hughes Medical Institute and Department of Biological Chemistry, University of California, Los Angeles, CA 90095-1662, USA.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Hurtado
authors.forename: E M
authors.initials: EM
authors.lastname: De Robertis
mesh_terms: D000557:Ambystoma / Q000196:embryology* / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000196:embryology / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D004627:Embryonic Induction / Q000235:genetics / Q000502:physiology*; D017403:In Situ Hybridization; D020935:MAP Kinase Signaling System; D009420:Nervous System / Q000196:embryology* / Q000378:metabolism; D020897:Organizers, Embryonic / Q000196:embryology*
chemical_list: D017931:DNA Primers