An E3 ubiquitin ligase, cullin-4 regulates retinal differentiation in Drosophila eye.
An E3 ubiquitin ligase, cullin-4 regulates retinal differentiation in Drosophila eye.
复制标题
DOI：
10.1002/dvg.23395
复制
发表时间：
2020-11
期刊：
影响因子：
1.5
通讯作者：
Singh, Amit
中科院分区：
文献类型：
--
作者：
Tare, Meghana;Chimata, Anuradha Venkatakrishnan;Gogia, Neha;Narwal, Sonia;Deshpande, Prajakta;Singh, Amit
在器官发生过程中，细胞增殖后特定细胞类型分化形成器官。任何分化异常都可能导致发育缺陷，从而导致器官几乎完全丧失。我们采用果蝇眼睛模型来了解分化过程中涉及的遗传和分子机制。在正向遗传筛选中，我们发现编码 E3 泛素连接酶的 cullin-4 (cul-4) 在视网膜分化中发挥重要作用。在发育过程中，cul-4 已知参与蛋白质降解、基因组稳定性调节和细胞周期调节。此前，我们报道了cul-4通过下调Wingless (Wg)/Wnt信号通路来调节眼睛发育过程中的细胞死亡。我们发现 cul-4 功能丧失会导致眼睛表型降低，这可能是由于细胞死亡的开始。然而，我们发现 cul-4 功能丧失也会通过下调 RD 基因表达来影响视网膜发育。视网膜分化的早期标记物在 cul-4 功能丧失的情况下失调，表明 cul-4 对于分化是必需的。此外，cul-4 的功能丧失会异位诱导眼睛发育负调节因子的表达，如 Wg 和 Homothorax (Hth)。在眼睛发育过程中，Wg 会阻止称为形态发生沟 (MF) 的同步分化波的进展。在 cul-4 功能丧失背景中，MF 标记 dpp-lacZ 的表达显着下调。我们的数据表明 cul-4 在视网膜分化中的新作用。这些研究可能对我们对早期眼睛发育的理解具有重要意义。
During organogenesis, cell proliferation is followed by the differentiation of specific cell types to form an organ. Any aberration in differentiation can result in developmental defects, which can result in a near-complete loss of an organ. We employ the Drosophila eye model to understand the genetic and molecular mechanisms involved in the process of differentiation. In a forward genetic screen, we identified, cullin-4 (cul-4), which encodes an E3 ubiquitin ligase, to play an important role in retinal differentiation. During development, cul-4 is known to be involved in protein degradation, regulation of genomic stability, and regulation of cell cycle. Previously, we have reported that cul-4 regulates cell death during eye development by downregulating Wingless (Wg)/ Wnt signaling pathway. We found that loss-of-function of cul-4 results in a reduced eye phenotype, which can be due to onset of cell death. However, we found that loss-of-function of cul-4 also affects retinal development by downregulating RD gene expression. Early markers of retinal differentiation are dysregulated in cul-4 loss of function conditions, indicating that cul-4 is necessary for differentiation. Furthermore, loss-of-function of cul-4 ectopically induces expression of negative regulators of eye development like Wg and Homothorax (Hth). During eye development, Wg is known to block the progression of a synchronous wave of differentiation referred to as Morphogenetic furrow (MF). In cul-4 loss-of-function background, expression of dpp-lacZ, a MF marker is significantly downregulated. Our data suggest a new role of cul-4 in retinal differentiation. These studies may have significant bearings on our understanding of early eye development.
登录
查看更多内容
影响因子：
4.6
作者：
Blair, SS
通讯作者：
Blair, SS
影响因子：
10.5
作者：
Bessa, J;Gebelein, B;Mann, RS
通讯作者：
Mann, RS
影响因子：
--
作者：
GARCIABELLIDO, A;MERRIAM, JR
通讯作者：
MERRIAM, JR
影响因子：
64.5
作者：
Braun S;Garcia JF;Rowley M;Rougemaille M;Shankar S;Madhani HD
通讯作者：
Madhani HD
影响因子：
2.3
作者：
Higa LA;Zhang H
通讯作者：
Zhang H