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Induction of the zebrafish ventral brain and floorplate requires cyclops/nodal signalling
K Sampath1, A L Rubinstein, A M Cheng
1Department of Cell Biology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
Abstract:
Zebrafish cyclops (cyc) mutations cause deficiencies in the dorsal mesendoderm and ventral neural tube, leading to neural defects and cyclopia. Here we report that cyc encodes a transforming growth factor-beta (TGF-beta)-related intercellular signalling molecule that is similar to mouse nodal. cyc is expressed in dorsal mesendoderm at gastrulation and in the prechordal plate until early somitogenesis. Expression reappears transiently in the left lateral-plate mesoderm, and in an unprecedented asymmetric pattern in the left forebrain. Injection of cyc RNA non-autonomously restores sonic hedgehog-expressing cells of the ventral brain and floorplate that are absent in cyc mutants, whereas inducing activities are abolished by cyc, a mutation of a conserved cysteine in the mature ligand. Our results indicate that cyc provides an essential non-cell-autonomous signal at gastrulation, leading to induction of the floorplate and ventral brain.
Insights
Zebrafish cyclops (cyc) mutations disrupt dorsal mesendoderm development, causing neural defects. This study identifies cyc as a TGF-beta signaling molecule essential for ventral brain and floorplate induction during gastrulation.
Area of Science:
- Developmental biology
- Molecular genetics
- Neuroscience
Background:
- Zebrafish cyclops (cyc) mutations lead to dorsal mesendoderm and ventral neural tube deficiencies.
- These deficiencies result in severe neural defects, including cyclopia.
Purpose of the Study:
- To identify the gene product of cyclops and elucidate its role in early embryonic development.
- To understand the molecular mechanisms underlying ventral brain and floorplate formation.
Main Methods:
- Characterization of the cyclops gene and its encoded protein.
- Analysis of cyc expression patterns during zebrafish embryogenesis.
- RNA injection experiments to rescue mutant phenotypes.
- Site-directed mutagenesis to investigate ligand function.
Main Results:
- cyc encodes a transforming growth factor-beta (TGF-beta)-related signaling molecule, similar to mouse nodal.
- cyc is expressed in the dorsal mesendoderm, prechordal plate, and asymmetrically in the left forebrain.
- cyc RNA injection rescues sonic hedgehog-expressing cells in the ventral brain and floorplate of cyc mutants.
- A mutation in a conserved cysteine residue abolishes the inducing activities of cyc.
Conclusions:
- cyc is crucial for non-cell-autonomous signaling during gastrulation.
- This signaling is essential for the induction of the floorplate and ventral brain structures.
- The findings provide insights into conserved mechanisms of vertebrate left-right patterning and neural development.