Waksman Institute and Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, NJ 08854, USA.
Waksman Institute and Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, NJ 08854, USA.
Curr Biol. 2019 Mar 4;29(5):856-864.e3. doi: 10.1016/j.cub.2019.01.044. Epub 2019 Feb 21.
Formation of correctly shaped organs is vital for normal function. The Drosophila wing has an elongated shape, which has been attributed in part to a preferential orientation of mitotic spindles along the proximal-distal axis [1, 2]. Orientation of mitotic spindles is believed to be a fundamental morphogenetic mechanism in multicellular organisms [3-6]. A contribution of spindle orientation to wing shape was inferred from observations that mutation of Dachsous-Fat pathway genes results in both rounder wings and loss of the normal proximal-distal bias in spindle orientation [1, 2, 7]. To directly evaluate the potential contribution of spindle orientation to wing morphogenesis, we assessed the consequences of loss of the Drosophila NuMA homolog Mud, which interacts with the dynein complex and has a conserved role in spindle orientation [8, 9]. Loss of Mud randomizes spindle orientation but does not alter wing shape. Analysis of growth and cell dynamics in developing discs and in ex vivo culture suggests that the absence of oriented cell divisions is compensated for by an increased contribution of cell rearrangements to wing shape. Our results indicate that oriented cell divisions are not required for wing morphogenesis, nor are they required for the morphogenesis of other Drosophila appendages. Moreover, our results suggest that normal organ shape is not achieved through locally specifying and then summing up individual cell behaviors, like oriented cell division. Instead, wing shape might be specified through tissue-wide stresses that dictate an overall arrangement of cells without specifying the individual cell behaviors needed to achieve it.
正确形成器官对于正常功能至关重要。果蝇的翅膀呈长形，这部分归因于有丝分裂纺锤体沿近端-远端轴的优先取向[1,2]。有丝分裂纺锤体的取向被认为是多细胞生物的基本形态发生机制[3-6]。由于观察到 Dachsous-Fat 途径基因突变会导致翅膀变圆，并且有丝分裂纺锤体取向失去正常的近端-远端偏倚[1,2,7]，因此推断纺锤体取向对翅膀形状有贡献。为了直接评估纺锤体取向对翅膀形态发生的潜在贡献，我们评估了果蝇 NuMA 同源物 Mud 缺失的后果，Mud 与动力蛋白复合物相互作用，在纺锤体取向中具有保守作用[8,9]。Mud 的缺失使纺锤体取向随机化，但不改变翅膀形状。对发育盘中的细胞生长和动力学以及体外培养的分析表明，定向细胞分裂的缺失被细胞重排对翅膀形状的更大贡献所补偿。我们的结果表明，定向细胞分裂对于翅膀形态发生不是必需的，对于其他果蝇附肢的形态发生也不是必需的。此外，我们的结果表明，正常器官形状不是通过局部指定然后累加单个细胞行为（如定向细胞分裂）来实现的。相反，翅膀形状可能通过组织范围的张力来指定，这些张力决定了细胞的整体排列，而无需指定实现该排列所需的个别细胞行为。
