Wood W, Turmaine M, Weber R, Camp V, Maki R A, McKercher S R, Martin P
Department of Anatomy and Developmental Biology, University College London, Gower St, London WC1E 6BT, UK.
Development. 2000 Dec;127(24):5245-52. doi: 10.1242/dev.127.24.5245.
Apoptosis is one of the key tools used by an embryo to regulate cell numbers and sculpt body shape. Although massive numbers of cells die during development, they are so rapidly phagocytosed that very few corpses are ever seen in most embryonic tissues. In this paper, we focus on the catastrophic cell death that occurs as the developing footplate is remodelled to transform webbed regions into free interdigital spaces. In the wild-type embryo, these dead cells are rapidly engulfed and cleared by macrophages. We show that in a macrophageless mouse embryo, null for the haemopoetic-lineage-specific transcription factor, PU.1, the task of phagocytosis is taken over by 'stand-in' mesenchymal neighbours in a clear example of cell redundancy. However, it takes three times as many of these mesenchymal phagocytes to complete the task and, at each stage of the clearance process - in the recognition of apoptotic debris, its engulfment and finally its digestion - they appear to be less efficient than macrophages. A molecular explanation for this may be that several of the engulfment genes expressed by macrophages, including the ABC1 transporter (believed to be part of the phagocytic machinery conserved from Caenorhabditis elegans to mouse), are not upregulated by these 'stand-in' phagocytes.
细胞凋亡是胚胎用于调节细胞数量和塑造身体形态的关键机制之一。尽管在发育过程中有大量细胞死亡，但它们被迅速吞噬，以至于在大多数胚胎组织中很少能看到细胞尸体。在本文中，我们关注的是在发育中的足板重塑过程中发生的灾难性细胞死亡，在此过程中蹼状区域转变为游离的趾间间隙。在野生型胚胎中，这些死亡细胞会迅速被巨噬细胞吞噬并清除。我们发现，在一种缺乏造血谱系特异性转录因子PU.1的无巨噬细胞小鼠胚胎中，吞噬任务由“替代”的间充质邻居接管，这是细胞冗余的一个明显例子。然而，这些间充质吞噬细胞完成任务所需的数量是巨噬细胞的三倍，并且在清除过程的每个阶段——从识别凋亡碎片、吞噬凋亡碎片到最终消化凋亡碎片——它们的效率似乎都低于巨噬细胞。对此的一种分子解释可能是，巨噬细胞表达的几种吞噬基因，包括ABC1转运蛋白（被认为是从秀丽隐杆线虫到小鼠保守的吞噬机制的一部分），并未被这些“替代”吞噬细胞上调表达。
