Biology Department, University of Detroit Mercy, Detroit, Michigan, USA.
Department of Physical and Life Sciences, Nevada State College, Henderson, Nevada, USA.
Fly (Austin). 2022 Dec;16(1):176-189. doi: 10.1080/19336934.2022.2062991.
Genetic screens are used in to identify genes key in the regulation of organismal development and growth. These screens have defined signalling pathways necessary for tissue and organismal development, which are evolutionarily conserved across species, including . Here, we have used an FLP/FRT mosaic system to screen for conditional regulators of cell growth and cell division in the eye. The conditional nature of this screen utilizes a block in the apoptotic pathway to prohibit the mosaic mutant cells from dying via apoptosis. From this screen, we identified two different mutants that mapped to the Hedgehog signalling pathway. Previously, we described a novel mutation and here we add to the understanding of disrupting the Hh pathway with a novel allele of . Both of these Hh components are negative regulators of the pathway, yet they depict mutant differences in the type of overgrowth created. mutations lead to overgrowth consisting of almost entirely wild-type tissue (non-autonomous overgrowth), while the mutation results in tissue that is overgrown in both the mutant and wild-type clones (both autonomous and non-autonomous). These differences in tissue overgrowth are consistent in the eye and wing. The observed difference is correlated with different deregulation patterns of pMad, the downstream effector of DPP signalling. This finding provides insight into pathway-specific differences that help to better understand intricacies of developmental processes and human diseases that result from deregulated Hedgehog signalling, such as basal cell carcinoma.
遗传筛选用于鉴定在调节生物发育和生长中起关键作用的基因。这些筛选定义了组织和生物发育所必需的信号通路，这些通路在包括果蝇在内的物种中是进化保守的。在这里，我们使用了一个 FLP/FRT 镶嵌系统，筛选果蝇眼睛中细胞生长和细胞分裂的条件调控因子。该筛选的条件性质利用凋亡途径中的一个阻断来防止镶嵌突变细胞通过凋亡死亡。从这个筛选中，我们鉴定了两个不同的突变体，它们映射到 Hedgehog 信号通路。以前，我们描述了一个新的 突变体，在这里我们增加了对破坏 Hh 通路的理解，引入了一个新的 突变等位基因。这两个 Hh 成分都是该通路的负调控因子，但它们在产生的过度生长类型上表现出突变差异。 突变导致几乎完全由野生型组织组成的过度生长（非自主过度生长），而 突变导致突变和野生型克隆都过度生长（自主和非自主）。这种组织过度生长的差异在果蝇的眼睛和翅膀中是一致的。观察到的差异与 DPP 信号下游效应物 pMad 的不同失调模式相关。这一发现为通路特异性差异提供了深入了解，有助于更好地理解发育过程的复杂性以及 Hedgehog 信号失调导致的人类疾病，如基底细胞癌。
