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Nodal signaling is required for closure of the anterior neural tube in zebrafish.

Aquilina-Beck A, Ilagan K, Liu Q, Liang JO - BMC Dev. Biol. (2007)

Bottom Line: N-cadherin expression and localization to the membrane are reduced in fish that lack Nodal signaling.Overexpression of an activated form of the TGFbeta Type I receptor Taram-A (Taram-A*) cell autonomously rescues mesendoderm formation in fish with a severe decrease in Nodal signaling.This work helps establish a role for Nodal signals in neurulation, and suggests that defects in Nodal signaling could underlie human neural tube defects such as exencephaly, a fatal condition characterized by an open neural tube in the anterior brain.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Biology, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH, USA. axa161@case.edu

ABSTRACT

Background: Nodals are secreted signaling proteins with many roles in vertebrate development. Here, we identify a new role for Nodal signaling in regulating closure of the rostral neural tube of zebrafish.

Results: We find that the neural tube in the presumptive forebrain fails to close in zebrafish Nodal signaling mutants. For instance, the cells that will give rise to the pineal organ fail to move from the lateral edges of the neural plate to the midline of the diencephalon. The open neural tube in Nodal signaling mutants may be due in part to reduced function of N-cadherin, a cell adhesion molecule expressed in the neural tube and required for neural tube closure. N-cadherin expression and localization to the membrane are reduced in fish that lack Nodal signaling. Further, N-cadherin mutants and morphants have a pineal phenotype similar to that of mutants with deficiencies in the Nodal pathway. Overexpression of an activated form of the TGFbeta Type I receptor Taram-A (Taram-A*) cell autonomously rescues mesendoderm formation in fish with a severe decrease in Nodal signaling. We find that overexpression of Taram-A* also corrects their open neural tube defect. This suggests that, as in mammals, the mesoderm and endoderm have an important role in regulating closure of the anterior neural tube of zebrafish.

Conclusion: This work helps establish a role for Nodal signals in neurulation, and suggests that defects in Nodal signaling could underlie human neural tube defects such as exencephaly, a fatal condition characterized by an open neural tube in the anterior brain.

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The ordered structure of the neural tube is disrupted in MZoep embryos. (A-H) Embryos were injected at the one cell stage with mGFP mRNA and imaged (A-F) live at 95% epiboly (95%), the 4–5 somite stage (4–5 s), the 10 somite stage (10 s), or (G, H) fixed at ~24 hpf. (A-F) Cross sections through the anterior developing neural plate, with presumptive eyes (e) indicated in panel B, the outer boundary of the neural tube indicated by a dotted line in panels B and C, and the midline indicated by the open arrowheads in C. (G, H) Horizontal sections through the midbrain and hindbrain of ~24 hpf embryos, with the midline of the brain (open arrowheads) and the otic vesicles (o) indicated in panel G. (I-J') Embryos were injected at the one cell stage with DNA encoding mGFP, raised to ~24 hpf, and imaged live in high magnification horizontal sections. Open arrowheads indicate elongated cells and the closed arrowheads indicate round cells. All images are confocal optical sections. Scale bars: 40 μm (A-H), 80 μm (I-J').
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Figure 6: The ordered structure of the neural tube is disrupted in MZoep embryos. (A-H) Embryos were injected at the one cell stage with mGFP mRNA and imaged (A-F) live at 95% epiboly (95%), the 4–5 somite stage (4–5 s), the 10 somite stage (10 s), or (G, H) fixed at ~24 hpf. (A-F) Cross sections through the anterior developing neural plate, with presumptive eyes (e) indicated in panel B, the outer boundary of the neural tube indicated by a dotted line in panels B and C, and the midline indicated by the open arrowheads in C. (G, H) Horizontal sections through the midbrain and hindbrain of ~24 hpf embryos, with the midline of the brain (open arrowheads) and the otic vesicles (o) indicated in panel G. (I-J') Embryos were injected at the one cell stage with DNA encoding mGFP, raised to ~24 hpf, and imaged live in high magnification horizontal sections. Open arrowheads indicate elongated cells and the closed arrowheads indicate round cells. All images are confocal optical sections. Scale bars: 40 μm (A-H), 80 μm (I-J').

Mentions: Consistent with previous studies, the neuroectoderm of WT embryos at 95% epiboly is in the form of a flat neural plate (Figure 6A). At the 4–5 somite stage, folding of the neural tube had started, giving the neuroepithelium the half circle appearance typical of the neural keel stage (Figure 6B). By the 10 somite stage, a round neural rod with a clear midline and a defined outer edge had formed (Figure 6C).


Nodal signaling is required for closure of the anterior neural tube in zebrafish.

Aquilina-Beck A, Ilagan K, Liu Q, Liang JO - BMC Dev. Biol. (2007)

The ordered structure of the neural tube is disrupted in MZoep embryos. (A-H) Embryos were injected at the one cell stage with mGFP mRNA and imaged (A-F) live at 95% epiboly (95%), the 4–5 somite stage (4–5 s), the 10 somite stage (10 s), or (G, H) fixed at ~24 hpf. (A-F) Cross sections through the anterior developing neural plate, with presumptive eyes (e) indicated in panel B, the outer boundary of the neural tube indicated by a dotted line in panels B and C, and the midline indicated by the open arrowheads in C. (G, H) Horizontal sections through the midbrain and hindbrain of ~24 hpf embryos, with the midline of the brain (open arrowheads) and the otic vesicles (o) indicated in panel G. (I-J') Embryos were injected at the one cell stage with DNA encoding mGFP, raised to ~24 hpf, and imaged live in high magnification horizontal sections. Open arrowheads indicate elongated cells and the closed arrowheads indicate round cells. All images are confocal optical sections. Scale bars: 40 μm (A-H), 80 μm (I-J').
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Related In: Results  -  Collection

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Figure 6: The ordered structure of the neural tube is disrupted in MZoep embryos. (A-H) Embryos were injected at the one cell stage with mGFP mRNA and imaged (A-F) live at 95% epiboly (95%), the 4–5 somite stage (4–5 s), the 10 somite stage (10 s), or (G, H) fixed at ~24 hpf. (A-F) Cross sections through the anterior developing neural plate, with presumptive eyes (e) indicated in panel B, the outer boundary of the neural tube indicated by a dotted line in panels B and C, and the midline indicated by the open arrowheads in C. (G, H) Horizontal sections through the midbrain and hindbrain of ~24 hpf embryos, with the midline of the brain (open arrowheads) and the otic vesicles (o) indicated in panel G. (I-J') Embryos were injected at the one cell stage with DNA encoding mGFP, raised to ~24 hpf, and imaged live in high magnification horizontal sections. Open arrowheads indicate elongated cells and the closed arrowheads indicate round cells. All images are confocal optical sections. Scale bars: 40 μm (A-H), 80 μm (I-J').
Mentions: Consistent with previous studies, the neuroectoderm of WT embryos at 95% epiboly is in the form of a flat neural plate (Figure 6A). At the 4–5 somite stage, folding of the neural tube had started, giving the neuroepithelium the half circle appearance typical of the neural keel stage (Figure 6B). By the 10 somite stage, a round neural rod with a clear midline and a defined outer edge had formed (Figure 6C).

Bottom Line: N-cadherin expression and localization to the membrane are reduced in fish that lack Nodal signaling.Overexpression of an activated form of the TGFbeta Type I receptor Taram-A (Taram-A*) cell autonomously rescues mesendoderm formation in fish with a severe decrease in Nodal signaling.This work helps establish a role for Nodal signals in neurulation, and suggests that defects in Nodal signaling could underlie human neural tube defects such as exencephaly, a fatal condition characterized by an open neural tube in the anterior brain.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Biology, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH, USA. axa161@case.edu

ABSTRACT

Background: Nodals are secreted signaling proteins with many roles in vertebrate development. Here, we identify a new role for Nodal signaling in regulating closure of the rostral neural tube of zebrafish.

Results: We find that the neural tube in the presumptive forebrain fails to close in zebrafish Nodal signaling mutants. For instance, the cells that will give rise to the pineal organ fail to move from the lateral edges of the neural plate to the midline of the diencephalon. The open neural tube in Nodal signaling mutants may be due in part to reduced function of N-cadherin, a cell adhesion molecule expressed in the neural tube and required for neural tube closure. N-cadherin expression and localization to the membrane are reduced in fish that lack Nodal signaling. Further, N-cadherin mutants and morphants have a pineal phenotype similar to that of mutants with deficiencies in the Nodal pathway. Overexpression of an activated form of the TGFbeta Type I receptor Taram-A (Taram-A*) cell autonomously rescues mesendoderm formation in fish with a severe decrease in Nodal signaling. We find that overexpression of Taram-A* also corrects their open neural tube defect. This suggests that, as in mammals, the mesoderm and endoderm have an important role in regulating closure of the anterior neural tube of zebrafish.

Conclusion: This work helps establish a role for Nodal signals in neurulation, and suggests that defects in Nodal signaling could underlie human neural tube defects such as exencephaly, a fatal condition characterized by an open neural tube in the anterior brain.

Show MeSH
Related in: MedlinePlus