Reduced cell number in the hindgut epithelium disrupts hindgut left–right asymmetry in a mutant of pebble, encoding a RhoGEF, in Drosophila embryos
Reduced cell number in the hindgut epithelium disrupts hindgut left–right asymmetry in a mutant of pebble, encoding a RhoGEF, in Drosophila embryos
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DOI：
10.1016/j.mod.2012.09.007
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发表时间：
2013-02
影响因子：
2.6
通讯作者：
Mitsutoshi Nakamura;Kenjiro Matsumoto;Yuta Iwamoto;T. Muguruma;Naotaka Nakazawa;Ryo Hatori;Kiichiro Taniguchi;Reo Maeda;K. Matsuno
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文献类型：
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作者：
Mitsutoshi Nakamura;Kenjiro Matsumoto;Yuta Iwamoto;T. Muguruma;Naotaka Nakazawa;Ryo Hatori;Kiichiro Taniguchi;Reo Maeda;K. Matsuno
动物的身体结构经常表现出左右（LR）不对称。在一些脊椎动物中，LR 对称性破坏的机制以及导致 LR 不对称发育的后续信号已被充分了解。然而，在无脊椎动物中，这些过程的分子基础很大程度上是未知的。因此，我们一直在研究果蝇LR不对称发育的遗传途径。胚胎肠道是果蝇发育过程中第一个表现出定向 LR 不对称性的器官。我们进行了基因筛选，以确定影响胚胎肠道 LR 不对称发育的突变。从这个屏幕中，我们分离出了卵石 (pbl)，它编码哺乳动物 RhoGEF 的同源物 Ect2。后肠的偏侧性在 pbl 无效突变体纯合胚胎中被随机化。 Pbl 是果蝇胞质分裂和上皮间质转化所需的多功能蛋白。与 Pbl 在胞质分裂中的作用一致，我们发现 pbl 纯合胚胎后肠上皮细胞数量减少。 pbl 在后肠上皮中的特异性表达，但在其他组织中没有，挽救了胚胎 pbl 纯合子中的 LR 缺陷并减少了细胞数量。 string 纯合胚胎 (stg) 是一种通过不同机制减少细胞数量的突变体，也显示出后肠的 LR 缺陷。然而，pbl突变体中细胞数量的减少并不伴随后肠上皮组织的规格或其完整性的缺陷。基于这些结果，我们推测细胞数量的减少可能是 pbl 后肠 LR 不对称缺陷的原因之一，尽管我们不能排除 Pbl 其他功能的贡献，包括通过其 RhoGEF 活性调节肌动蛋白细胞骨架。
Animals often show left–right (LR) asymmetry in their body structures. In some vertebrates, the mechanisms underlying LR symmetry breaking and the subsequent signals responsible for LR asymmetric development are well understood. However, in invertebrates, the molecular bases of these processes are largely unknown. Therefore, we have been studying the genetic pathway of LR asymmetric development in Drosophila. The embryonic gut is the first organ that shows directional LR asymmetry during Drosophila development. We performed a genetic screen to identify mutations affecting LR asymmetric development of the embryonic gut. From this screen, we isolated pebble (pbl), which encodes a homolog of a mammalian RhoGEF, Ect2. The laterality of the hindgut was randomized in embryos homozygous for a null mutant of pbl. Pbl is a multi-functional protein required for cytokinesis and the epithelial-to-mesenchymal transition in Drosophila. Consistent with Pbl’s role in cytokinesis, we found reduced numbers of cells in the hindgut epithelium in pbl homozygous embryos. The specific expression of pbl in the hindgut epithelium, but not in other tissues, rescued the LR defects and reduced cell number in embryonic pbl homozygotes. Embryos homozygous for string (stg), a mutant that reduces cell number through a different mechanism, also showed LR defects of the hindgut. However, the reduction in cell number in the pbl mutants was not accompanied by defects in the specification of hindgut epithelial tissues or their integrity. Based on these results, we speculate that the reduction in cell number may be one reason for the LR asymmetry defect of the pbl hindgut, although we cannot exclude contributions from other functions of Pbl, including regulation of the actin cytoskeleton through its RhoGEF activity.