WHEN THE LEGS OF CHICKENS AND MICE WERE RESTRAINED IN THE EGG OR THE WOMB, BONE DEVELOPMENT PROCEEDED IMPROPERLY, AS SEEN HERE. Many expectant parents have had a moment (and sometimes many more) of panic when their baby stops moving in the womb. The fact that babies need to move, and long stillness is a sign that something's wrong, is well known, but the reasons why have not been fully understood until now. Part of the answer was already known: movement in the womb helps an embryo develop the strong bones and joints it will need when exposed to the harsher environment of the outside world. The missing piece has been how this occurs on a cellular level, but a paper in Development provides an answer. Our first cells are totipotent, meaning they can become any sort of tissue or organ in the body. Clearly, as we grow it is very important that they become the right ones – sometimes teeth or muscles grow inside the testicles or ovaries and, unsurprisingly, the body can't cope with too much of this. The signals required to make sure the appropriate cells form in the right places are complex. Professor Paula Murphy of Trinity College, Dublin, and fellow authors studied the process in chickens and mice, but Murphy expressed confidence that the mechanisms are the same for other warm-blooded creatures, including humans. They found regular movement is essential if cells are to know whether to form cartilage or bone. “Our new findings show that in the absence of embryonic movement the cells that should form articular cartilage receive incorrect molecular signals, where one type of signal is lost while another inappropriate signal is activated in its place,” Murphy said in a statement. “In short, the cells receive the signal that says ‘make bone’ when they should receive the signal that says ‘make cartilage’.” In the paper, Murphy describes the cellular processes that turn regular movement into messages on the type of transformation a cell needs to undergo. The difference between turning to bone or cartilage is controlled by the expression or suppression of multiple genes. Two different signaling processes, know as Wnt and BMP, are required, but they malfunction when the embryo is immobilized, with some downstream processes reduced while others occur too strongly. Particularly, movements of the leg activate the delightfully named Smurf1 gene, which, rather than turning people blue, produces an enzyme that, among other functions, insulates the joints against excessive signaling that would produce bone where cartilage should be. It is hoped the work will increase our capacity to use stem cells to restore cartilage after injuries – a lucrative market from sports stars desperate to get back on the field as quickly as possible. Even more importantly, it might be used to treat people with degenerative diseases of the joints, including many forms of arthritis. Source
