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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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N-cad expression in the anterior neural keel is altered in MZoep mutants. (A-F) N-cad immunostaining of tissue sections from WT and MZoep embryos. (A, B) Sagittal sections though the anterior neural keel with anterior to the left and dorsal to the top. (C-D') Parasagittal sections with anterior to the left and dorsal to the top. Panels C' and D' are higher magnifications of the boxed regions in panels C and D, respectively. Arrows point to N-cad labeling in the cell membrane, while the arrowhead indicates labeling in the cytoplasm. (E, F) Transverse sections through the anterior neural tube, dorsal to the top. n ≥ 30 embryos for each sample. Embryos are at 95–100% epiboly (95–100%) or the 5–6 somite stage (5–6 s). Scale bars: 40 μm (C, D, E, F), 20 μm (A, B, C', D').
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Figure 5: N-cad expression in the anterior neural keel is altered in MZoep mutants. (A-F) N-cad immunostaining of tissue sections from WT and MZoep embryos. (A, B) Sagittal sections though the anterior neural keel with anterior to the left and dorsal to the top. (C-D') Parasagittal sections with anterior to the left and dorsal to the top. Panels C' and D' are higher magnifications of the boxed regions in panels C and D, respectively. Arrows point to N-cad labeling in the cell membrane, while the arrowhead indicates labeling in the cytoplasm. (E, F) Transverse sections through the anterior neural tube, dorsal to the top. n ≥ 30 embryos for each sample. Embryos are at 95–100% epiboly (95–100%) or the 5–6 somite stage (5–6 s). Scale bars: 40 μm (C, D, E, F), 20 μm (A, B, C', D').

Mentions: To explore the relationship between Nodal signaling and cell adhesion, N-cad expression was compared between MZoep and control embryos. Age-matched controls were produced by mating rescued oep/oep females with oep/+ males, resulting in clutches of eggs that were 50% oep/+ and 50% MZoep, or by comparing clutches of WT and MZoep embryos that were fertilized at the same time. No change in the levels of n-cad mRNA could be detected between MZoep and WT embryos processed in parallel for whole mount in situ hybridization (data not shown). However, N-cad immunostaining on tissue sections showed that protein expression patterns were altered (Figure 5).


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)

N-cad expression in the anterior neural keel is altered in MZoep mutants. (A-F) N-cad immunostaining of tissue sections from WT and MZoep embryos. (A, B) Sagittal sections though the anterior neural keel with anterior to the left and dorsal to the top. (C-D') Parasagittal sections with anterior to the left and dorsal to the top. Panels C' and D' are higher magnifications of the boxed regions in panels C and D, respectively. Arrows point to N-cad labeling in the cell membrane, while the arrowhead indicates labeling in the cytoplasm. (E, F) Transverse sections through the anterior neural tube, dorsal to the top. n ≥ 30 embryos for each sample. Embryos are at 95–100% epiboly (95–100%) or the 5–6 somite stage (5–6 s). Scale bars: 40 μm (C, D, E, F), 20 μm (A, B, C', D').
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2214732&req=5

Figure 5: N-cad expression in the anterior neural keel is altered in MZoep mutants. (A-F) N-cad immunostaining of tissue sections from WT and MZoep embryos. (A, B) Sagittal sections though the anterior neural keel with anterior to the left and dorsal to the top. (C-D') Parasagittal sections with anterior to the left and dorsal to the top. Panels C' and D' are higher magnifications of the boxed regions in panels C and D, respectively. Arrows point to N-cad labeling in the cell membrane, while the arrowhead indicates labeling in the cytoplasm. (E, F) Transverse sections through the anterior neural tube, dorsal to the top. n ≥ 30 embryos for each sample. Embryos are at 95–100% epiboly (95–100%) or the 5–6 somite stage (5–6 s). Scale bars: 40 μm (C, D, E, F), 20 μm (A, B, C', D').
Mentions: To explore the relationship between Nodal signaling and cell adhesion, N-cad expression was compared between MZoep and control embryos. Age-matched controls were produced by mating rescued oep/oep females with oep/+ males, resulting in clutches of eggs that were 50% oep/+ and 50% MZoep, or by comparing clutches of WT and MZoep embryos that were fertilized at the same time. No change in the levels of n-cad mRNA could be detected between MZoep and WT embryos processed in parallel for whole mount in situ hybridization (data not shown). However, N-cad immunostaining on tissue sections showed that protein expression patterns were altered (Figure 5).

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