Connecting muscle development, birth defects, and evolution: An essential role for muscle connective tissue

Skeletal muscle powers all movement of the vertebrate body and is distributed in multiple regions that have evolved distinct functions. Axial muscles are ancestral muscles essential for support and locomotion of the whole body. The evolution of the head was accompanied by development of cranial muscles essential for eye movement, feeding, vocalization, and facial expression. With the evolution of paired fins and limbs and their associated muscles, vertebrates gained increased locomotor agility, populated the land, and acquired fine motor skills. Finally, unique muscles with specialized functions have evolved in some groups, and the diaphragm which solely evolved in mammals to increase respiratory capacity is one such example. The function of all these muscles requires their integration with the other components of the musculoskeletal system: muscle connective tissue (MCT), tendons, bones as well as nerves and vasculature. MCT is muscle's closest anatomical and functional partner. Not only is MCT critical in the adult for muscle structure and function, but recently MCT in the embryo has been found to be crucial for muscle development. In this review, we examine the important role of the MCT in axial, head, limb, and diaphragm muscles for regulating normal muscle development, discuss how defects in MCT-muscle interactions during development underlie the etiology of a range of birth defects, and explore how changes in MCT development or communication with muscle may have led to the modification and acquisition of new muscles during vertebrate evolution.