Defective adult oligodendrocyte and Schwann cell development, pigment pattern, and craniofacial morphology in puma mutant zebrafish having an alpha tubulin mutation.
Defective adult oligodendrocyte and Schwann cell development, pigment pattern, and craniofacial morphology in puma mutant zebrafish having an alpha tubulin mutation.
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DOI：
10.1016/j.ydbio.2010.07.035
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发表时间：
2010-10-15
影响因子：
2.7
通讯作者：
Parichy DM
中科院分区：
文献类型：
--
作者：
Larson TA;Gordon TN;Lau HE;Parichy DM
髓鞘形成的过程仍然不完全了解，但由于人类已知的几种髓鞘形成障碍和脱髓鞘疾病，具有深刻的生物医学意义。在这里，我们分析了斑马鱼美洲狮突变体，最初分离的色素模式缺陷仅限于成人阶段。我们发现美洲狮突变体还具有外周神经系统施万细胞的迟发性缺陷、运动异常以及成人颅面形态的性别偏见缺陷。使用定位克隆的方法，我们确定了一个关键的遗传间隔窝藏两个α微管蛋白基因座，我们确定了化学诱导的错义突变，在这些之一，微管蛋白α 8-样3A（tuba 8l 3A）。我们证明了tuba 8l 3a在中枢神经系统（CNS）中的表达，导致我们寻找少突胶质细胞（CNS的髓鞘形成细胞）发育中的缺陷。我们发现，在成年美洲狮突变体的中枢神经系统髓鞘和少突胶质细胞数量的总减少，这些赤字是显而易见的，在幼虫到成人的转化。相比之下，胚胎和早期幼虫的分析揭示了一个正常的少突胶质细胞的补充，但未能本地化正常量的髓鞘碱性蛋白（MBP）mRNA的细胞过程中，并未能组织这些过程中的野生型。这项研究确定了美洲狮突变体作为一个有价值的模型，用于研究微管依赖的髓鞘形成事件，以及在成人髓鞘再生的策略。
The processes of myelination remain incompletely understood but are of profound biomedical importance owing to the several dysmyelinating and demyelinating disorders known in humans. Here, we analyze the zebrafish puma mutant, isolated originally for pigment pattern defects limited to the adult stage. We show that puma mutants also have late-arising defects in Schwann cells of the peripheral nervous system, locomotor abnormalities, and sex-biased defects in adult craniofacial morphology. Using methods of positional cloning, we identify a critical genetic interval harboring two alpha tubulin loci, and we identify a chemically induced missense mutation in one of these, tubulin alpha 8-like 3a (tuba8l3a). We demonstrate tuba8l3a expression in the central nervous system (CNS), leading us to search for defects in the development of oligodendrocytes, the myelinating cells of the CNS. We find gross reductions in CNS myelin and oligodendrocyte numbers in adult puma mutants, and these deficits are apparent already during the larval-to-adult transformation. By contrast, analyses of embryos and early larvae reveal a normal complement of oligodendrocytes that nevertheless fail to localize normal amounts of myelin basic protein (mbp) mRNA in cellular processes, and fail to organize these processes as in the wild-type. This study identifies the puma mutant as a valuable model for studying microtubule-dependent events of myelination, as well as strategies for remyelination in the adult.
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DOI：
10.1093/brain/awn076
发表时间：
2008-07
期刊：
Brain : a journal of neurology
影响因子：
--
作者：
Dubois-Dalcq M;Williams A;Stadelmann C;Stankoff B;Zalc B;Lubetzki C
通讯作者：
Lubetzki C
影响因子：
64.5
作者：
Keays DA;Tian G;Poirier K;Huang GJ;Siebold C;Cleak J;Oliver PL;Fray M;Harvey RJ;Molnár Z;Piñon MC;Dear N;Valdar W;Brown SD;Davies KE;Rawlins JN;Cowan NJ;Nolan P;Chelly J;Flint J
通讯作者：
Flint J
影响因子：
4.2
作者：
Galiano, M. R.;Andrieux, A.;Hallak, M. E.
通讯作者：
Hallak, M. E.
影响因子：
3.3
作者：
Ballestrem, C;Wehrle-Haller, B;Imhof, BA
通讯作者：
Imhof, BA
影响因子：
14.9
作者：
HALL, JL;COWAN, NJ
通讯作者：
COWAN, NJ