Melvin Moss’ function matrix theory—Revisited

The functional matrix theory was first introduced in the orthodontic literature by Melvin Moss half century ago. Since its original introduction, several attempts have been made to test the validity of this theory with mixed results. In this paper, we present evidence generated using transgenic mice to test the role of neuronal function in craniofacial development. Our data confirmed previous observations that midface retrusion accompanied neuronal dysfunction in the HexB−/− mouse model of Sandhoff disease. Importantly, restoration of neuronal function after targeted expression of a therapeutic gene selectively in the neurons of HexB−/− mice resulted in normalization of midface development in this mouse model. Histological analysis of the cranial base revealed that abnormal development of the synchondroses underlies the attendant midface retrusion in this model: Neuronal dysfunction led to the absence of hypertrophic chondrocytes in the synchondroses, whereas restoration of neuronal function resulted in normalization of the cranial base development. Taken together, our studies suggest that neuronal function is critical for normal midface development, underscoring the importance of the functional matrix theory as originally proposed by Melvin Moss.