Abca12-mediated lipid transport and Snap29-dependent trafficking of lamellar granules are crucial for epidermal morphogenesis in a zebrafish model of ichthyosis.
Abca12-mediated lipid transport and Snap29-dependent trafficking of lamellar granules are crucial for epidermal morphogenesis in a zebrafish model of ichthyosis.
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DOI：
10.1242/dmm.007146
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发表时间：
2011-11
影响因子：
4.3
通讯作者：
Uitto J
中科院分区：
文献类型：
--
作者：
Li Q;Frank M;Akiyama M;Shimizu H;Ho SY;Thisse C;Thisse B;Sprecher E;Uitto J
斑马鱼（Danio rerio）可以作为研究遗传性皮肤病的模型系统。在胚胎生长的最初5-6天，皮肤迅速发育，伴随着皮肤特异性基因的表达。野生型斑马鱼第5天的透射电子显微镜（TEM）显示，两细胞层表皮与下面的胶原基质由一层基底膜分离，半粒发育完全。扫描电子显微镜（SEM）显示角质形成细胞具有离散微脊的有序表面轮廓。为了深入了解表皮形态发生，我们采用了morpholino介导的abca12和snap29基因的敲低，这两个基因分别对脂质分泌和层状颗粒的细胞内运输至关重要。当将Morpholinos置于外显子-内含子连接处时，将其注射到一至四细胞期的胚胎中，其阻止相应基因表达的有效性为90%。第3天，abca12变形体的透射电镜显示含有脂质的电子致密片层颗粒积聚，而snap29变形体的表皮则出现明显的空泡。通过扫描电镜对表皮形态发生的评估显示，在两种情况下，角化细胞表面的微脊结构和针状突起的发育都受到了类似的干扰。这些形态学发现类似于丑角鱼鳞病和CEDNIK综合征的表皮变化，这两种疾病分别是由ABCA12和SNAP29基因突变引起的常染色体隐性角化疾病。结果表明，干预表皮脂质转运的独立通路可导致表皮形态发生表型上类似的扰动，这些鱼类突变体可以作为研究这些角化疾病的病理机制的模型。
Zebrafish (Danio rerio) can serve as a model system to study heritable skin diseases. The skin is rapidly developed during the first 5–6 days of embryonic growth, accompanied by expression of skin-specific genes. Transmission electron microscopy (TEM) of wild-type zebrafish at day 5 reveals a two-cell-layer epidermis separated from the underlying collagenous stroma by a basement membrane with fully developed hemidesmosomes. Scanning electron microscopy (SEM) reveals an ordered surface contour of keratinocytes with discrete microridges. To gain insight into epidermal morphogenesis, we have employed morpholino-mediated knockdown of the abca12 and snap29 genes, which are crucial for secretion of lipids and intracellular trafficking of lamellar granules, respectively. Morpholinos, when placed on exon-intron junctions, were >90% effective in preventing the corresponding gene expression when injected into one- to four-cell-stage embryos. By day 3, TEM of abca12 morphants showed accumulation of lipid-containing electron-dense lamellar granules, whereas snap29 morphants showed the presence of apparently empty vesicles in the epidermis. Evaluation of epidermal morphogenesis by SEM revealed similar perturbations in both cases in the microridge architecture and the development of spicule-like protrusions on the surface of keratinocytes. These morphological findings are akin to epidermal changes in harlequin ichthyosis and CEDNIK syndrome, autosomal recessive keratinization disorders due to mutations in the ABCA12 and SNAP29 genes, respectively. The results indicate that interference of independent pathways involving lipid transport in the epidermis can result in phenotypically similar perturbations in epidermal morphogenesis, and that these fish mutants can serve as a model to study the pathomechanisms of these keratinization disorders.
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影响因子：
9.8
作者：
Sprecher, E;Ishida-Yamamoto, A;Mandel, H
通讯作者：
Mandel, H
影响因子：
2.5
作者：
KIMMEL, CB;BALLARD, WW;SCHILLING, TF
通讯作者：
SCHILLING, TF
影响因子：
10.7
作者：
SAITOU, N;NEI, M
通讯作者：
NEI, M
影响因子：
--
作者：
Brown, Sara J.;Irvine, Alan D.
通讯作者：
Irvine, Alan D.
影响因子：
3.7
作者：
Rapaport D;Lugassy Y;Sprecher E;Horowitz M
通讯作者：
Horowitz M