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Glial cell line-derived neurotrophic factor promotes the survival of multiple neuron types in the central and peripheral nervous system. Moreover, it plays a key role in the development of the enteric nervous system and in the kidney organogenesis. Glial cell line-derived neurotrophic factor and their receptors are expressed in the developing tooth as well as in the trigeminal ganglion. However, the precise role of this growth factor in tooth morphogenesis and cell differentiation, or in the development of trigeminal ganglion cells, is still elusive. Using structural and ultrastructural techniques we analyzed in detail the first molar tooth germ of glial cell line-derived neurotrophic factor deficient mice as well as the neuronal density in trigeminal ganglion. The length and width of first molar tooth germ in knockout deficient animals showed no differences in the knockout animals in comparison with age-matched heterozygous or wild-type littermates. Nevertheless, in mice lacking glial cell line-derived neurotrophic factor, both ameloblasts and odontoblasts failed to fully develop and differentiate, and the enamel matrix and predentin layers were absent. On the other hand, the number of trigeminal sensory neurons and the structure of the nerves supplying first molar tooth germ were largely normal. Present results suggest a new non-neuronal role for glial cell line-derived neurotrophic factor in tooth development. Glial cell line-derived neurotrophic factor seems not to be involved in tooth initiation and morphogenesis, whereas it seems essential for cytodifferentiation. Conversely, neither development of trigeminal neuron nor nerve fibers supplying teeth are directly dependent on glial cell line-derived neutrophic factor.

The rat dorsal root ganglia (DRG) contain heterogeneous subpopulations of sensory neurons as demonstrated by ultrastructural, histochemical and immunohistochemical methods. In this study we investigated whether phenotypic heterogeneity occurs in the distribution of protein gene product 9.5 (PGP 9.5) in DRG neurons of adult rats by combined immunohistochemical and image analysis (neuron-size and intensity of immunostaining) techniques. Moreover, the effect of different fixatives on the expression of PGP 9.5 was analyzed. PGP 9.5 immunoreactivity (IR) was observed in all primary sensory neurons and in the axons of the ganglionic nerve fibres, but not in the satellite glial cells or Schwann cells. Data from a quantitative study demonstrated that DRG neurons displayed a homogeneous pattern of PGP 9.5 IR which was not affected by fixatives, and no correlation between neuron size and intensity of immunostaining was encountered. Thus, as reported for other neuronal and neuroendocrine cell proteins, no heterogeneity exists in the phenotypic expression of immunohistochemically demonstrable PGP 9.5 in sensory neurons of the adult rat DRG.