Muscle and its connective tissue are intimately linked during embryogenesis and adult life. Thus, interactions between these tissues might be crucial for their development. To date, the lack of molecular markers for connective tissue fibroblasts has hindered the study of these potentially important interactions, but now, on , Gabrielle Kardon and colleagues identify the transcription factor Tcf4 as a marker for connective tissue fibroblasts and reveal that connective tissue is an important regulator of myogenesis. By making Tcf4GFPCre mice, which allow genetic manipulation of connective tissue fibroblasts, they show that these fibroblasts regulate both muscle fibre type and maturation. In addition, the researchers unexpectedly discover that low levels of Tcf4 in myogenic cells promote the overall maturation of muscle fibre type. These and other data identify novel extrinsic and intrinsic mechanisms that regulate myogenesis and show for the first time that connective tissue is a vital component of the niche that controls muscle development.
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