Vertebrate skeletogenesis

Abstract

Vertebrate skeletogenesis consists in elaborating an edifice of more than 200 pieces of bone and cartilage. Each skeletal piece is crafted at a distinct location in the body, is articulated with others, and reaches a specific size, shape, and tissue composition according to both species instructions and individual determinants. This complex, customized body frame fulfills multiple essential tasks. It confers morphological features, allows controlled postures and movements, protects vital organs, houses hematopoiesis, stores minerals, and adsorbs toxins. This review provides an overview of the multiple facets of this ingenious process for experts as well as nonexperts of skeletogenesis. We explain how the developing vertebrate uses both specific and ubiquitously expressed genes to generate multipotent mesenchymal cells, specify them to a skeletogenic fate, control their survival and proliferation, and direct their differentiation into cartilage, bone, and joint cells. We review milestone discoveries made toward uncovering the intricate networks of regulatory factors that are involved in these processes, with an emphasis on signaling pathways and transcription factors. We describe numerous skeletal malformation and degeneration diseases that occur in humans as a result of mutations in regulatory genes, and explain how these diseases both help and motivate us to further decipher skeletogenic processes. Upon discussing current knowledge and gaps in knowledge in the control of skeletogenesis, we highlight ultimate research goals and propose research priorities and approaches for future endeavors.