A novel role for MAPKAPK2 in morphogenesis during zebrafish development.
A novel role for MAPKAPK2 in morphogenesis during zebrafish development.
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DOI：
10.1371/journal.pgen.1000413
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发表时间：
2009-03
期刊：
影响因子：
4.5
通讯作者：
Mullins MC
中科院分区：
文献类型：
--
作者：
Holloway BA;Gomez de la Torre Canny S;Ye Y;Slusarski DC;Freisinger CM;Dosch R;Chou MM;Wagner DS;Mullins MC
One of the earliest morphogenetic processes in the development of many animals is epiboly. In the zebrafish, epiboly ensues when the animally localized blastoderm cells spread, thin over, and enclose the vegetally localized yolk. Only a few factors are known to function in this fundamental process. We identified a maternal-effect mutant, betty boop (bbp), which displays a novel defect in epiboly, wherein the blastoderm margin constricts dramatically, precisely when half of the yolk cell is covered by the blastoderm, causing the yolk cell to burst. Whole-blastoderm transplants and mRNA microinjection rescue demonstrate that Bbp functions in the yolk cell to regulate epiboly. We positionally cloned the maternal-effect bbp mutant gene and identified it as the zebrafish homolog of the serine-threonine kinase Mitogen Activated Protein Kinase Activated Protein Kinase 2, or MAPKAPK2, which was not previously known to function in embryonic development. We show that the regulation of MAPKAPK2 is conserved and p38 MAP kinase functions upstream of MAPKAPK2 in regulating epiboly in the zebrafish embryo. Dramatic alterations in calcium dynamics, together with the massive marginal constrictive force observed in bbp mutants, indicate precocious constriction of an F-actin network within the yolk cell, which first forms at 50% epiboly and regulates epiboly progression. We show that MAPKAPK2 activity and its regulator p38 MAPK function in the yolk cell to regulate the process of epiboly, identifying a new pathway regulating this cell movement process. We postulate that a p38 MAPKAPK2 kinase cascade modulates the activity of F-actin at the yolk cell margin circumference allowing the gradual closure of the blastopore as epiboly progresses. One of the earliest cell movement processes in the development of many animals is epiboly. In the zebrafish, epiboly ensues when the blastoderm cells spread over and enclose the yolk cell. Only a few factors are known to function in this fundamental process. We identified a maternal-effect mutant, betty boop (bbp), which displays a novel defect in epiboly, wherein the blastoderm margin constricts dramatically, precisely when half of the yolk cell is covered by the blastoderm, causing the yolk cell to burst. We demonstrate that Bbp functions in the yolk cell to regulate epiboly. We positionally cloned the bbp mutant gene and identified it as the serine-threonine kinase Mitogen Activated Protein Kinase Activated Protein Kinase 2, or MAPKAPK2, which was not previously known to function in embryonic development. We show that the regulation of MAPKAPK2 is conserved within a p38 MAP kinase pathway, thus identifying a new pathway in the regulation of this fundamental cell movement process. We postulate that a p38 MAPKAPK2 kinase cascade modulates F-actin contraction at the yolk cell margin circumference, allowing the gradual closure of the cells over the yolk cell as epiboly progresses.
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