title: GSK-3 activity is critical for the orientation of the cortical microtubules and the dorsoventral axis determination in zebrafish embryos.
abstract: The formation of dorsal-ventral (D-V) axis is the earliest event that breaks the radial symmetry and determines the bilateral body plan of a vertebrate embryo, however, the maternal control of this process is not fully understood. Here, we discovered a new dorsalizing window of acute lithium treatment, which covers only less than 10 minutes after fertilization. Lithium treatment in this window was not able to reverse the ventralized phenotype in tokkeabi (tkk) mutant embryos, and its dorsalizing activity on wild-type embryos was inhibited by nocodazole co-treatment. These evidences indicate that the underlying mechanism is independent of a direct activation of Wnt/β-catenin signaling, but depends on the upstream level of the microtubule mediated dorsal determinant transport. In order to identify the target of lithium in this newly discovered sensitive window, GSK-3 inhibitor IX as well as the IMPase inhibitor L690, 330 treatments were performed. We found that only GSK-3 inhibitor IX treatment mimicked the lithium treatment in the dorsalizing activity. Further study showed that the parallel pattern of cortical microtubules in the vegetal pole region and the directed migration of the Wnt8a mRNA were randomized by either lithium or GSK-3 inhibitor IX treatment. These results thus revealed an early and critical role of GSK-3 activity that regulates the orientation of the cortical microtubules and the directed transport of the dorsal determinants in zebrafish embryos.
authors.affiliation: Key Laboratory of Experimental Teratology of the Ministry of Education, Life Science College, Shandong University, Jinan, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Shao
authors.forename: Yushuang
authors.initials: Y
authors.lastname: Lin
authors.forename: Zhongzhen
authors.initials: Z
authors.lastname: Liu
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Lifeng
authors.initials: L
authors.lastname: Wang
authors.forename: Changbin
authors.initials: C
authors.lastname: Liu
authors.forename: Hongwei
authors.initials: H
authors.lastname: Zhang
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000166:cytology* / Q000187:drug effects / Q000196:embryology / Q000201:enzymology*; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008094:Lithium / Q000494:pharmacology; D008297:Male; D008870:Microtubules / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D009035:Mothers; D009068:Movement / Q000187:drug effects; D010063:Ovum / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012399:Rotation; D015398:Signal Transduction / Q000187:drug effects; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
chemical_list: D003598:Cytoskeletal Proteins; D012333:RNA, Messenger; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin; C094521:wnt8a protein, zebrafish; D008094:Lithium; D038362:Glycogen Synthase Kinase 3