Celebrating the centennial of the most famous experiment in embryology: Hilde Mangold, Hans Spemann and the organizer

De Robertis, Edward M.; Driever, Wolfgang; Mayor, Roberto

doi:10.1016/j.cdev.2024.203921

Cells & Development

2024

DOI: 10.1016/j.cdev.2024.203921

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Celebrating the centennial of the most famous experiment in embryology: Hilde Mangold, Hans Spemann and the organizer

Edward M. De Robertis,

Wolfgang Driever,

Roberto Mayor

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2024

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“…This region induces the formation of the central nervous system (CNS) and dorsal mesoderm structures such as somite and kidney ( 3 ). This pioneering experiment was the basis for our current understanding of vertebrate development as a series of cell–cell inductive interactions, and its centennial is being celebrated this year ( 4 ). With the advent of molecular cloning, many genes encoding proteins secreted by the organizer were isolated.…”

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Molecular analysis of a self-organizing signaling pathway for Xenopus axial patterning from egg to tailbud

Azbazdar,

De Robertis

2024

Proc. Natl. Acad. Sci. U.S.A.

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Xenopus embryos provide a favorable material to dissect the sequential steps that lead to dorsal–ventral (D-V) and anterior–posterior (A-P) cell differentiation. Here, we analyze the signaling pathways involved in this process using loss-of-function and gain-of-function approaches. The initial step was provided by Hwa, a transmembrane protein that robustly activates early β-catenin signaling when microinjected into the ventral side of the embryo leading to complete twinned axes. The following step was the activation of Xenopus Nodal-related growth factors, which could rescue the depletion of β-catenin and were themselves blocked by the extracellular Nodal antagonists Cerberus-Short and Lefty. During gastrulation, the Spemann–Mangold organizer secretes a cocktail of growth factor antagonists, of which the BMP antagonists Chordin and Noggin could rescue simultaneously D-V and A-P tissues in β-catenin-depleted embryos. Surprisingly, this rescue occurred in the absence of any β-catenin transcriptional activity as measured by β-catenin activated Luciferase reporters. The Wnt antagonist Dickkopf (Dkk1) strongly synergized with the early Hwa signal by inhibiting late Wnt signals. Depletion of Sizzled (Szl), an antagonist of the Tolloid chordinase, was epistatic over the Hwa and Dkk1 synergy. BMP4 mRNA injection blocked Hwa-induced ectopic axes, and Dkk1 inhibited BMP signaling late, but not early, during gastrulation. Several unexpected findings were made, e.g., well-patterned complete embryonic axes are induced by Chordin or Nodal in β-catenin knockdown embryos, dorsalization by Lithium chloride (LiCl) is mediated by Nodals, Dkk1 exerts its anteriorizing and dorsalizing effects by regulating late BMP signaling, and the Dkk1 phenotype requires Szl.

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mentioning

confidence: 99%

Molecular analysis of a self-organizing signaling pathway for Xenopus axial patterning from egg to tailbud

Azbazdar,

De Robertis

2024

Proc. Natl. Acad. Sci. U.S.A.

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Celebrating the centennial of the most famous experiment in embryology: Hilde Mangold, Hans Spemann and the organizer

Cited by 1 publication

References 11 publications

Molecular analysis of a self-organizing signaling pathway for Xenopus axial patterning from egg to tailbud

Molecular analysis of a self-organizing signaling pathway for Xenopus axial patterning from egg to tailbud

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