Mesenchymal cells engulf and clear apoptotic footplate cells in macrophageless PU.1 null mouse embryos

Apoptosis is one of the key tools used by an embryo to regulate cell number s and sculpt body shape. Although massive numbers of cells die during devel opment, they are so rapidly phagocytosed that very few corpses are ever see n in most embryonic tissues. In this paper, we focus on the catastrophic ce ll death that occurs as the developing footplate is remodelled to transform webbed regions into free interdigital spaces. In the wild-type embryo, the se dead cells are rapidly engulfed and cleared by macrophages. We show that in a macrophageless mouse embryo, null for the haemopoetic-lineage-specifi c transcription factor, PU.1, the task of phagocytosis is taken over by 'st and-in' mesenchymal neighbours in a dear example of cell redundancy. Howeve r, 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 t o 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 cons erved from Caenorhabditis elegans to mouse), are not upregulated by these ' stand-in' phagocytes.