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Mutation of pescadillo disrupts oligodendrocyte formation in zebrafish.

Simmons T, Appel B - PLoS ONE (2012)

Bottom Line: During embryogenesis, ventral neural tube precursors give rise to oligodendrocyte progenitor cells, which divide and migrate throughout the central nervous system.We found that pescadillo function is required for both the proper number of oligodendrocyte progenitors to form, by regulating cell cycle progression, and for normal levels of myelin gene expression.Our data provide evidence that neural precursors require pes function to progress through the cell cycle and produce oligodendrocyte progenitor cells and for oligodendrocyte differentiation.

View Article: PubMed Central - PubMed

Affiliation: Department of Biological Sciences, Vanderbilt University, Nashville, Tennessee, United States of America.

ABSTRACT

Background: In vertebrates, the myelin sheath is essential for efficient propagation of action potentials along the axon shaft. Oligodendrocytes are the cells of the central nervous system that create myelin sheaths. During embryogenesis, ventral neural tube precursors give rise to oligodendrocyte progenitor cells, which divide and migrate throughout the central nervous system. This study aimed to investigate mechanisms that regulate oligodendrocyte progenitor cell formation.

Methodology/principal findings: By conducting a mutagenesis screen in transgenic zebrafish, we identified a mutation, designated vu166, by an apparent reduction in the number of oligodendrocyte progenitor cells in the dorsal spinal cord. We subsequently determined that vu166 is an allele of pescadillo, a gene known to play a role in ribosome biogenesis and cell proliferation. We found that pescadillo function is required for both the proper number of oligodendrocyte progenitors to form, by regulating cell cycle progression, and for normal levels of myelin gene expression.

Conclusions/significance: Our data provide evidence that neural precursors require pes function to progress through the cell cycle and produce oligodendrocyte progenitor cells and for oligodendrocyte differentiation.

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Related in: MedlinePlus

Loss of pes function disrupts progression of spinal cord cells through the cell cycle.(A) The time required to progress from S-phase to M-phase in the spinal cord is shown by the ratio of PH-3+/BrdU+ to total PH-3+ cells at the indicated time points after a BrdU pulse. (B) The length of S-phase in the spinal cord is shown by the ratio of BrdU+/EdU+ cells to total BrdU+ cells at the indicated time points after a BrdU pulse. Wild-type (blue) and pes166−/− (red) are shown. (C,D) Transverse sections through spinal cords of 4 dpf wild-type (C) and mutant (D) larvae processed for in situ RNA hybridization showing the expression of the neural precursor marker sox2.
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pone-0032317-g005: Loss of pes function disrupts progression of spinal cord cells through the cell cycle.(A) The time required to progress from S-phase to M-phase in the spinal cord is shown by the ratio of PH-3+/BrdU+ to total PH-3+ cells at the indicated time points after a BrdU pulse. (B) The length of S-phase in the spinal cord is shown by the ratio of BrdU+/EdU+ cells to total BrdU+ cells at the indicated time points after a BrdU pulse. Wild-type (blue) and pes166−/− (red) are shown. (C,D) Transverse sections through spinal cords of 4 dpf wild-type (C) and mutant (D) larvae processed for in situ RNA hybridization showing the expression of the neural precursor marker sox2.

Mentions: An alternative explanation is that pes function is necessary for cell cycle progression. To test this idea, we investigated the cell cycle kinetics of pes larvae. To determine the length of time that spinal cord cells spend in S/G2 phase, we performed a BrdU pulse-chase experiment in which larvae were labeled with BrdU and then fixed at various time-points followed by co-labeling with anti-BrdU and anti-PH3 antibodies. By finding the period of time that it took for BrdU+ cells to become labeled with PH-3, we calculated the time it took them to progress from S-phase to mitosis. Our results indicate that whereas spinal cord cells of wild-type larvae progressed from labeling to M phase within roughly six hours, mutant larvae had cells that were still entering mitosis as long as 10 hours after the pulse, the longest interval we collected (Figure 5A).


Mutation of pescadillo disrupts oligodendrocyte formation in zebrafish.

Simmons T, Appel B - PLoS ONE (2012)

Loss of pes function disrupts progression of spinal cord cells through the cell cycle.(A) The time required to progress from S-phase to M-phase in the spinal cord is shown by the ratio of PH-3+/BrdU+ to total PH-3+ cells at the indicated time points after a BrdU pulse. (B) The length of S-phase in the spinal cord is shown by the ratio of BrdU+/EdU+ cells to total BrdU+ cells at the indicated time points after a BrdU pulse. Wild-type (blue) and pes166−/− (red) are shown. (C,D) Transverse sections through spinal cords of 4 dpf wild-type (C) and mutant (D) larvae processed for in situ RNA hybridization showing the expression of the neural precursor marker sox2.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3285679&req=5

pone-0032317-g005: Loss of pes function disrupts progression of spinal cord cells through the cell cycle.(A) The time required to progress from S-phase to M-phase in the spinal cord is shown by the ratio of PH-3+/BrdU+ to total PH-3+ cells at the indicated time points after a BrdU pulse. (B) The length of S-phase in the spinal cord is shown by the ratio of BrdU+/EdU+ cells to total BrdU+ cells at the indicated time points after a BrdU pulse. Wild-type (blue) and pes166−/− (red) are shown. (C,D) Transverse sections through spinal cords of 4 dpf wild-type (C) and mutant (D) larvae processed for in situ RNA hybridization showing the expression of the neural precursor marker sox2.
Mentions: An alternative explanation is that pes function is necessary for cell cycle progression. To test this idea, we investigated the cell cycle kinetics of pes larvae. To determine the length of time that spinal cord cells spend in S/G2 phase, we performed a BrdU pulse-chase experiment in which larvae were labeled with BrdU and then fixed at various time-points followed by co-labeling with anti-BrdU and anti-PH3 antibodies. By finding the period of time that it took for BrdU+ cells to become labeled with PH-3, we calculated the time it took them to progress from S-phase to mitosis. Our results indicate that whereas spinal cord cells of wild-type larvae progressed from labeling to M phase within roughly six hours, mutant larvae had cells that were still entering mitosis as long as 10 hours after the pulse, the longest interval we collected (Figure 5A).

Bottom Line: During embryogenesis, ventral neural tube precursors give rise to oligodendrocyte progenitor cells, which divide and migrate throughout the central nervous system.We found that pescadillo function is required for both the proper number of oligodendrocyte progenitors to form, by regulating cell cycle progression, and for normal levels of myelin gene expression.Our data provide evidence that neural precursors require pes function to progress through the cell cycle and produce oligodendrocyte progenitor cells and for oligodendrocyte differentiation.

View Article: PubMed Central - PubMed

Affiliation: Department of Biological Sciences, Vanderbilt University, Nashville, Tennessee, United States of America.

ABSTRACT

Background: In vertebrates, the myelin sheath is essential for efficient propagation of action potentials along the axon shaft. Oligodendrocytes are the cells of the central nervous system that create myelin sheaths. During embryogenesis, ventral neural tube precursors give rise to oligodendrocyte progenitor cells, which divide and migrate throughout the central nervous system. This study aimed to investigate mechanisms that regulate oligodendrocyte progenitor cell formation.

Methodology/principal findings: By conducting a mutagenesis screen in transgenic zebrafish, we identified a mutation, designated vu166, by an apparent reduction in the number of oligodendrocyte progenitor cells in the dorsal spinal cord. We subsequently determined that vu166 is an allele of pescadillo, a gene known to play a role in ribosome biogenesis and cell proliferation. We found that pescadillo function is required for both the proper number of oligodendrocyte progenitors to form, by regulating cell cycle progression, and for normal levels of myelin gene expression.

Conclusions/significance: Our data provide evidence that neural precursors require pes function to progress through the cell cycle and produce oligodendrocyte progenitor cells and for oligodendrocyte differentiation.

Show MeSH
Related in: MedlinePlus