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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 expanded and divided pineal phenotype is present in n-cad mutants and morphants. (A-C) Homozygous pac mutants were fixed at 30 hpf, and then processed for in situ hybridization with an antisense probe for otx5. Dorsal views with anterior to the top. pac mutants could have a (A) normal, round-shaped pineal morphology, (B) an elongated pineal anlage or (C) a divided pineal. (D-G) Embryos were injected at the one to four cell stage, fixed at 74 hpf, and then assayed for expression of otx5. Frontal views with dorsal to the top. The presumptive pineal organ (arrowheads) forms (D) a single domain in control embryos and a (E-G) divided pineal in embryos depleted in N-cad through morpholino (MO) injections. Scale bars: 30 μm (A-C), 100 μm (D-G).
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Figure 4: The expanded and divided pineal phenotype is present in n-cad mutants and morphants. (A-C) Homozygous pac mutants were fixed at 30 hpf, and then processed for in situ hybridization with an antisense probe for otx5. Dorsal views with anterior to the top. pac mutants could have a (A) normal, round-shaped pineal morphology, (B) an elongated pineal anlage or (C) a divided pineal. (D-G) Embryos were injected at the one to four cell stage, fixed at 74 hpf, and then assayed for expression of otx5. Frontal views with dorsal to the top. The presumptive pineal organ (arrowheads) forms (D) a single domain in control embryos and a (E-G) divided pineal in embryos depleted in N-cad through morpholino (MO) injections. Scale bars: 30 μm (A-C), 100 μm (D-G).

Mentions: The cell surface protein N-cad is required for adhesion between cells of the zebrafish neuroepithelium. In zebrafish parachute (pac)/n-cad mutants, the convergent extension movements that shape the neural plate are altered and the dorsal neural tube fails to close [28,29]. Expression of otx5 in pac mutants revealed a strikingly similar range of pineal phenotypes to those found in sqt mutants. The presumptive pineal could be round, elongated, or divided (Figure 4A–C). The abnormal pineal phenotypes were found at a higher rate in glass onion (glo) embryos, which are more severely affected n-cad mutants (Table 1). Further, antisense morpholino (MO) mediated depletion of N-cad resulted in a divided pineal phenotype (Figure 4D–G). The presence of the divided pineal in pac/n-cad/glo mutants and n-cad morphants suggests there could be a connection between Nodal and N-cad.


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 expanded and divided pineal phenotype is present in n-cad mutants and morphants. (A-C) Homozygous pac mutants were fixed at 30 hpf, and then processed for in situ hybridization with an antisense probe for otx5. Dorsal views with anterior to the top. pac mutants could have a (A) normal, round-shaped pineal morphology, (B) an elongated pineal anlage or (C) a divided pineal. (D-G) Embryos were injected at the one to four cell stage, fixed at 74 hpf, and then assayed for expression of otx5. Frontal views with dorsal to the top. The presumptive pineal organ (arrowheads) forms (D) a single domain in control embryos and a (E-G) divided pineal in embryos depleted in N-cad through morpholino (MO) injections. Scale bars: 30 μm (A-C), 100 μm (D-G).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 4: The expanded and divided pineal phenotype is present in n-cad mutants and morphants. (A-C) Homozygous pac mutants were fixed at 30 hpf, and then processed for in situ hybridization with an antisense probe for otx5. Dorsal views with anterior to the top. pac mutants could have a (A) normal, round-shaped pineal morphology, (B) an elongated pineal anlage or (C) a divided pineal. (D-G) Embryos were injected at the one to four cell stage, fixed at 74 hpf, and then assayed for expression of otx5. Frontal views with dorsal to the top. The presumptive pineal organ (arrowheads) forms (D) a single domain in control embryos and a (E-G) divided pineal in embryos depleted in N-cad through morpholino (MO) injections. Scale bars: 30 μm (A-C), 100 μm (D-G).
Mentions: The cell surface protein N-cad is required for adhesion between cells of the zebrafish neuroepithelium. In zebrafish parachute (pac)/n-cad mutants, the convergent extension movements that shape the neural plate are altered and the dorsal neural tube fails to close [28,29]. Expression of otx5 in pac mutants revealed a strikingly similar range of pineal phenotypes to those found in sqt mutants. The presumptive pineal could be round, elongated, or divided (Figure 4A–C). The abnormal pineal phenotypes were found at a higher rate in glass onion (glo) embryos, which are more severely affected n-cad mutants (Table 1). Further, antisense morpholino (MO) mediated depletion of N-cad resulted in a divided pineal phenotype (Figure 4D–G). The presence of the divided pineal in pac/n-cad/glo mutants and n-cad morphants suggests there could be a connection between Nodal and N-cad.

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