An essential role of variant histone H3.3 for ectomesenchyme potential of the cranial neural crest.
An essential role of variant histone H3.3 for ectomesenchyme potential of the cranial neural crest.
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变体组蛋白 H3.3 对颅神经嵴外间质潜能的重要作用。
DOI：
10.1371/journal.pgen.1002938
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发表时间：
2012-09
期刊：
影响因子：
4.5
通讯作者：
Crump JG
中科院分区：
文献类型：
--
作者：
Cox SG;Kim H;Garnett AT;Medeiros DM;An W;Crump JG
神经脊(NC)是一种脊椎动物特有的细胞群，具有显著的多能性。尽管颅骨NC细胞来源于神经板边缘(NPB)外胚层，但它不仅对周围神经系统有贡献，而且对头部骨骼的外胚间充质前体也有贡献。到目前为止，这种广泛潜力的发展基础仍然难以捉摸。在这里，我们证明了替换的组蛋白H3.3是这些细胞在早期发育过程中产生外胚间充质和头部色素前体所必需的。在斑马鱼的正向遗传筛查中，我们在H3F3A中发现了一个显性的D123N突变，H3F3A是斑马鱼组蛋白H3.3基因的五个变异体之一，它消除了计算机数控系统衍生的头部骨骼和一部分色素细胞，但保持了其他计算机控制系统衍生产品和躯干NC的完整。核小体组装分析表明，突变体D123N H3.3通过形成异常的H3同源二聚体来干扰H3.3核小体的掺入。与染色质中H3.3掺入不足引起的Cnc缺陷一致，供应外源野生型H3.3拯救了突变体的头部骨骼发育。令人惊讶的是，显性突变体H3.3在整个胚胎范围内的表达对Cnc外的胚胎发育几乎没有影响，这表明Cnc对H3.3整合中的缺陷具有出人意料的特异性敏感性。尽管之前的研究表明H3.3参与了在胚系发育过程中产生全能性的大规模组蛋白替换事件，但我们的工作揭示了H3.3在外胚层衍生的NC的广泛潜力中的额外作用，包括制造头部骨骼的中胚层样外胚间充质前体的能力。脊椎动物头部的进化在很大程度上是由于一个新的细胞群体--脑神经脊的出现。这些细胞对头部的不同结构做出了贡献，包括头骨的大部分，然而神经脊细胞如何在发育过程中获得如此广泛的潜力仍然是一个谜。通过研究缺乏神经脊源性头骨的突变斑马鱼，我们发现这些细胞的异常潜力取决于包装它们DNA的一种组蛋白的“H3.3”版本。我们认为，DNA包装的戏剧性变化是允许脊细胞在脊椎动物头部制造各种新细胞类型的关键一步。
The neural crest (NC) is a vertebrate-specific cell population that exhibits remarkable multipotency. Although derived from the neural plate border (NPB) ectoderm, cranial NC (CNC) cells contribute not only to the peripheral nervous system but also to the ectomesenchymal precursors of the head skeleton. To date, the developmental basis for such broad potential has remained elusive. Here, we show that the replacement histone H3.3 is essential during early CNC development for these cells to generate ectomesenchyme and head pigment precursors. In a forward genetic screen in zebrafish, we identified a dominant D123N mutation in h3f3a, one of five zebrafish variant histone H3.3 genes, that eliminates the CNC–derived head skeleton and a subset of pigment cells yet leaves other CNC derivatives and trunk NC intact. Analyses of nucleosome assembly indicate that mutant D123N H3.3 interferes with H3.3 nucleosomal incorporation by forming aberrant H3 homodimers. Consistent with CNC defects arising from insufficient H3.3 incorporation into chromatin, supplying exogenous wild-type H3.3 rescues head skeletal development in mutants. Surprisingly, embryo-wide expression of dominant mutant H3.3 had little effect on embryonic development outside CNC, indicating an unexpectedly specific sensitivity of CNC to defects in H3.3 incorporation. Whereas previous studies had implicated H3.3 in large-scale histone replacement events that generate totipotency during germ line development, our work has revealed an additional role of H3.3 in the broad potential of the ectoderm-derived CNC, including the ability to make the mesoderm-like ectomesenchymal precursors of the head skeleton. The evolution of the vertebrate head was made possible in large part by the emergence of a new cell population, the cranial neural crest. These cells contribute to diverse structures of the head, including most of the skull, yet how neural crest cells acquire such broad potential during development has remained a mystery. By studying mutant zebrafish that lack the neural-crest-derived skull, we find that the unusual potential of these cells depends on an “H3.3” version of one of the histone proteins that package their DNA. We propose then that a dramatic change in the packaging of DNA is a key step in allowing crest cells to make a wide range of new cell types in the vertebrate head.
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影响因子：
64.8
作者：
Hajkova, Petra;Ancelin, Katia;Waldmann, Tanja;Lacoste, Nicolas;Lange, Ulrike C.;Cesari, Francesca;Lee, Caroline;Almouzni, Genevieve;Schneider, Robert;Surani, M. Azim
通讯作者：
Surani, M. Azim
影响因子：
9.8
作者：
Crump JG;Swartz ME;Kimmel CB
通讯作者：
Kimmel CB
影响因子：
64.5
作者：
Goldberg AD;Banaszynski LA;Noh KM;Lewis PW;Elsaesser SJ;Stadler S;Dewell S;Law M;Guo X;Li X;Wen D;Chapgier A;DeKelver RC;Miller JC;Lee YL;Boydston EA;Holmes MC;Gregory PD;Greally JM;Rafii S;Yang C;Scambler PJ;Garrick D;Gibbons RJ;Higgs DR;Cristea IM;Urnov FD;Zheng D;Allis CD
通讯作者：
Allis CD
影响因子：
2.5
作者：
KIMMEL, CB;BALLARD, WW;SCHILLING, TF
通讯作者：
SCHILLING, TF
影响因子：
2.7
作者：
Ignatius, Myron S.;Moose, Holly E.;Henion, Paul D.
通讯作者：
Henion, Paul D.