Abstract
Our aim is to critically review current knowledge of the function and regulation of cell death in the developing limb. We provide a detailed, but short, overview of the areas of cell death observed in the developing limb, establishing their function in morphogenesis and structural development of limb tissues. We will examine the functions of this process in the formation and growth of the limb primordia, formation of cartilaginous skeleton, formation of synovial joints, and establishment of muscle bellies, tendons, and entheses. We will analyze the plasticity of the cell death program by focusing on the developmental potential of progenitors prior to death. Considering the prolonged plasticity of progenitors to escape from the death process, we will discuss a new biological perspective that explains cell death: this process, rather than secondary to a specific genetic program, is a consequence of the tissue building strategy employed by the embryo based on the formation of scaffolds that disintegrate once their associated neighboring structures differentiate.
Highlights
The brilliant and clear-sighted review by Glücksmann[1] in 1951 proposing a new interpretation of previous descriptive studies reporting the occurrence of dying cells in the tissues of vertebrate embryos is a milestone in research in this field
Among others, of John Saunders and John Fallon in the United States, Jean Milaire in Belgium, and Donald Ede and J Richard Hinchliffe in the UK, the developing vertebrate limb became a paradigm for studying embryonic cell death
The proposal of a distinctive and specific type of cell death in tissue remodeling, termed “apoptosis,”[2] along with the identification of an evolutionarily conserved genetic cascade activated in the embryonic death process,[3,4] consolidated the view of embryonic cell death as a distinctive and regulated developmental process
Summary
The brilliant and clear-sighted review by Glücksmann[1] in 1951 proposing a new interpretation of previous descriptive studies reporting the occurrence of dying cells in the tissues of vertebrate embryos is a milestone in research in this field. Apoptosis has been discarded as a “unique” cell death mechanism in embryonic tissues, and the genetic regulators of cell death appeared to be related with the degenerative cascades activated in dying cells rather than being master regulators of developmental processes.[5,6] The aim of this report is to critically review current knowledge of cell death in the developing limb to propose a new perspective for the biological significance of cell death in embryonic systems
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