Luis Pouchucq , Cristian A. Undurraga , Ricardo Fuentes , Mauricio Cornejo , Miguel L. Allende , Octavio Monasterio
{"title":"γ-微管蛋白小复合物的形成对斑马鱼早期胚胎发生至关重要","authors":"Luis Pouchucq , Cristian A. Undurraga , Ricardo Fuentes , Mauricio Cornejo , Miguel L. Allende , Octavio Monasterio","doi":"10.1016/j.mod.2018.06.006","DOIUrl":null,"url":null,"abstract":"<div><p>The centrosomal protein γ-tubulin is part of the cytoplasmic γ-tubulin small (γ-TuSCs) and large complexes (γ-TuRCs). Both, molecular and cellular evidence indicate that γ-tubulin plays a central role in microtubule nucleation and mitotic spindle formation. However, the molecular mechanisms of complex formation and subsequent biological roles in animal development remain unclear. Here, we used γ-tubulin gene knockdown in the zebrafish early embryo model to gain insights into its activity and cellular contribution during vertebrate embryogenesis. γ-Tubulin loss-of-function impaired γ-TuSC formation, impacting the microtubule nucleation rate <em>in vitro</em>. Moreover, decreased γ-tubulin synthesis caused dramatic defects in nuclear dynamics and cell cycle progression, leading to developmental arrest at the mid-gastrula stage. At the subcellular level, microtubule organization and function were altered, affecting chromosome segregation and triggering cell proliferation arrest and apoptosis. Our results suggest that <em>de novo</em> translated γ-tubulin participates in γ-TuSC formation required for early animal development. Importantly, formation of this complex is essential for both centrosome assembly and function, and cell proliferation. Thus, γ-TuSC integrity appears to be critical for cell cycle progression, and concomitantly, for coordinating the many distinct activities carried out by the early embryo. Our findings identify a novel role for γ-TuSC in the regulation of early vertebrate embryogenesis, providing molecular and biochemical starting points for future in depth studies of γ-tubulin functionality and its specific role in development.</p></div>","PeriodicalId":49844,"journal":{"name":"Mechanisms of Development","volume":"154 ","pages":"Pages 145-152"},"PeriodicalIF":2.6000,"publicationDate":"2018-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.mod.2018.06.006","citationCount":"3","resultStr":"{\"title\":\"γ-Tubulin small complex formation is essential for early zebrafish embryogenesis\",\"authors\":\"Luis Pouchucq , Cristian A. Undurraga , Ricardo Fuentes , Mauricio Cornejo , Miguel L. Allende , Octavio Monasterio\",\"doi\":\"10.1016/j.mod.2018.06.006\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>The centrosomal protein γ-tubulin is part of the cytoplasmic γ-tubulin small (γ-TuSCs) and large complexes (γ-TuRCs). Both, molecular and cellular evidence indicate that γ-tubulin plays a central role in microtubule nucleation and mitotic spindle formation. However, the molecular mechanisms of complex formation and subsequent biological roles in animal development remain unclear. Here, we used γ-tubulin gene knockdown in the zebrafish early embryo model to gain insights into its activity and cellular contribution during vertebrate embryogenesis. γ-Tubulin loss-of-function impaired γ-TuSC formation, impacting the microtubule nucleation rate <em>in vitro</em>. Moreover, decreased γ-tubulin synthesis caused dramatic defects in nuclear dynamics and cell cycle progression, leading to developmental arrest at the mid-gastrula stage. At the subcellular level, microtubule organization and function were altered, affecting chromosome segregation and triggering cell proliferation arrest and apoptosis. Our results suggest that <em>de novo</em> translated γ-tubulin participates in γ-TuSC formation required for early animal development. Importantly, formation of this complex is essential for both centrosome assembly and function, and cell proliferation. Thus, γ-TuSC integrity appears to be critical for cell cycle progression, and concomitantly, for coordinating the many distinct activities carried out by the early embryo. Our findings identify a novel role for γ-TuSC in the regulation of early vertebrate embryogenesis, providing molecular and biochemical starting points for future in depth studies of γ-tubulin functionality and its specific role in development.</p></div>\",\"PeriodicalId\":49844,\"journal\":{\"name\":\"Mechanisms of Development\",\"volume\":\"154 \",\"pages\":\"Pages 145-152\"},\"PeriodicalIF\":2.6000,\"publicationDate\":\"2018-12-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://sci-hub-pdf.com/10.1016/j.mod.2018.06.006\",\"citationCount\":\"3\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Mechanisms of Development\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0925477318300613\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"Medicine\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Mechanisms of Development","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0925477318300613","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"Medicine","Score":null,"Total":0}
γ-Tubulin small complex formation is essential for early zebrafish embryogenesis
The centrosomal protein γ-tubulin is part of the cytoplasmic γ-tubulin small (γ-TuSCs) and large complexes (γ-TuRCs). Both, molecular and cellular evidence indicate that γ-tubulin plays a central role in microtubule nucleation and mitotic spindle formation. However, the molecular mechanisms of complex formation and subsequent biological roles in animal development remain unclear. Here, we used γ-tubulin gene knockdown in the zebrafish early embryo model to gain insights into its activity and cellular contribution during vertebrate embryogenesis. γ-Tubulin loss-of-function impaired γ-TuSC formation, impacting the microtubule nucleation rate in vitro. Moreover, decreased γ-tubulin synthesis caused dramatic defects in nuclear dynamics and cell cycle progression, leading to developmental arrest at the mid-gastrula stage. At the subcellular level, microtubule organization and function were altered, affecting chromosome segregation and triggering cell proliferation arrest and apoptosis. Our results suggest that de novo translated γ-tubulin participates in γ-TuSC formation required for early animal development. Importantly, formation of this complex is essential for both centrosome assembly and function, and cell proliferation. Thus, γ-TuSC integrity appears to be critical for cell cycle progression, and concomitantly, for coordinating the many distinct activities carried out by the early embryo. Our findings identify a novel role for γ-TuSC in the regulation of early vertebrate embryogenesis, providing molecular and biochemical starting points for future in depth studies of γ-tubulin functionality and its specific role in development.
期刊介绍:
Mechanisms of Development is an international journal covering the areas of cell biology and developmental biology. In addition to publishing work at the interphase of these two disciplines, we also publish work that is purely cell biology as well as classical developmental biology.
Mechanisms of Development will consider papers in any area of cell biology or developmental biology, in any model system like animals and plants, using a variety of approaches, such as cellular, biomechanical, molecular, quantitative, computational and theoretical biology.
Areas of particular interest include:
Cell and tissue morphogenesis
Cell adhesion and migration
Cell shape and polarity
Biomechanics
Theoretical modelling of cell and developmental biology
Quantitative biology
Stem cell biology
Cell differentiation
Cell proliferation and cell death
Evo-Devo
Membrane traffic
Metabolic regulation
Organ and organoid development
Regeneration
Mechanisms of Development does not publish descriptive studies of gene expression patterns and molecular screens; for submission of such studies see Gene Expression Patterns.