The Neurotrophic Influence on Craniofacial Development Subsequent to in Utero Unilateral Transection of the Trigeminal(V) Nerve

Abstract

Transection of the root (sensory and motor) of the trigeminal(V) nerve and/or Gasserian ganglion was produced unilaterally in Long-Evans rat fetuses in utero at 17.5, 18.5, and 19.5 days of gestation to delineate the role of the trigeminal(V) nerve in the regulation of cellular differentiation, tissue morphogenesis, subsequent development and growth, and maintenance of the craniofacial complex. This research is believed to be the first time that such a procedure has been attempted on a mammalian fetus. Each animal was clinically evaluated and then sacrificed at specific intervals between birth and 75 days postnatally. Methods of evaluation included gross observations of physical appearance and neurological condition, histology (i.e., light microscopy), cephalograms, and ossified tissue staining of whole specimens. Transection of the trigeminal(V) nerve did not result in an absence or inhibition of morphogenesis and development of the craniofacial elements (i.e., skeletal). The results indicate that attainment of cellular differentiation and fundamental form of skeletal elements, including the temporomandibular joint, are inherent (i.e., genetic) and independent of both functional demand and biomechanical factors. Normal growth and maturation of the skeletal components were achieved without neural innervation; however, maintenance of the functional skeletal form, of the proliferating progenitor cells of the secondary cartilage of the temporomandibular joint, and of minor skeletal morphogenetic features (e.g., origin and insertion of muscle) were at least partially dependent upon the presence of functional musculature and local mechanical stimuli. Since development and subsequent growth of the mandible did occur without neuromuscular innervation, the secondary cartilage of the temporomandibular joint probably constitutes a center of adaptive and compensatory growth. Even though the neuromuscular junctions (i.e., motor) were prevented from normally developing after birth, no craniofacial asymmetries were noted at l day postnatally. Expected craniofacial asymmetries of muscle mass and skeletal elements did result after 14 days postnatally due to abnormal functional compensation from a developing occlusion. Animals with transection of both the root and Gasserian ganglion of the trigeminal(V) nerve were not distinguishable clinically or histologically from those animals exhibiting only the transection of the root. The lack of neural innervation appeared to have no discernible effect on the initiation of tooth germ tissues in specific tissue interactions, the synthesis of extracellular matrices of hard and soft dental tissues, the spatial relationship of tooth germs in alveolar bone, the development of the periodontium, and the process of eruption. The trigeminal(V) nerve does not directly influence or regulate the primary initiation, spatial positioning, cellular differentiation, tissue morphogenesis or fundamental form, development, and subsequent growth of skeletal tissues; therefore, it is not a major mechanism of regulation of craniofacial skeletal morphogenesis and development.