Retinal vascular disease and the pathogenesis of facioscapulohumeral muscular dystrophy. A signalling message from Wnt?

The peripheral retinal vascular abnormality which accompanies FSHD belongs morphologically and clinically to a class of developmental 'retinal hypovasculopathies' caused by abnormalities of 'Wnt' signalling, which controls retinal angiogenesis. Wnt signalling is also fundamental to myogenesis. This paper integrates modern concepts of myogenic cell signalling and of transcription factor expression and control with data from the classic early ophthalmic and myology embryology literature. Together, they support an hypothesis that abnormalities of Wnt signalling, which activates myogenic programs and transcription factors in myoblasts and satellite cells, leads to defective muscle regeneration in FSHD. The selective vulnerability of different FSHD muscles (notably facial muscle, from the second branchial arch) might reflect patterns of transcription factor redundancies. This hypothesis has implications for FSHD research through study of transcription factors patterning in normal human muscles, and for autologous cell transplantation.