CABD, CSIC/Universidad Pablo de Olavide, Seville, Spain.
ALMIA, CABD, CSIC/Universidad Pablo de Olavide, Seville, Spain.
PLoS Biol. 2024 Jan 30;22(1):e3002450. doi: 10.1371/journal.pbio.3002450. eCollection 2024 Jan.
Biological processes are intrinsically noisy, and yet, the result of development-like the species-specific size and shape of organs-is usually remarkably precise. This precision suggests the existence of mechanisms of feedback control that ensure that deviations from a target size are minimized. Still, we have very limited understanding of how these mechanisms operate. Here, we investigate the problem of organ size precision using the Drosophila eye. The size of the adult eye depends on the rates at which eye progenitor cells grow and differentiate. We first find that the progenitor net growth rate results from the balance between their proliferation and apoptosis, with this latter contributing to determining both final eye size and its variability. In turn, apoptosis of progenitor cells is hampered by Dpp, a BMP2/4 signaling molecule transiently produced by early differentiating retinal cells. Our genetic and computational experiments show how the status of retinal differentiation is communicated to progenitors through the differentiation-dependent production of Dpp, which, by adjusting the rate of apoptosis, exerts a feedback control over the net growth of progenitors to reduce final eye size variability.
生物过程本质上是嘈杂的，但发育的结果——如器官的物种特异性大小和形状——通常非常精确。这种精确性表明存在反馈控制机制，以确保目标大小的偏差最小化。尽管如此，我们对这些机制如何运作的了解非常有限。在这里，我们使用果蝇眼睛来研究器官大小精度的问题。成年眼睛的大小取决于眼祖细胞生长和分化的速度。我们首先发现，祖细胞的净生长速率是由它们的增殖和凋亡之间的平衡决定的，后者有助于确定最终眼睛的大小及其可变性。反过来，祖细胞的凋亡又受到 Dpp 的阻碍，Dpp 是一种由早期分化的视网膜细胞短暂产生的 BMP2/4 信号分子。我们的遗传和计算实验表明，视网膜分化的状态是如何通过 Dpp 的分化依赖性产生来传递给祖细胞的，Dpp 通过调节凋亡的速度，对祖细胞的净生长施加反馈控制，从而减少最终眼睛大小的可变性。
