Abstract
Nerve growth factor (NGF) is important for the development and the differentiation of neuronal and non-neuronal cells. NGF binds to specific low- and high-affinity cell surface receptors, respectively, p75NTR and TrkA. In the present study, we examined by immunohistochemistry the expression patterns of the NGF, p75NTR, and TrkA proteins during human fetal tooth development, in order to better understand the mode of NGF signaling action in dental tissues. The results obtained show that these molecules are expressed in a wide range of dental cells of both epithelial and mesenchymal origin during early stages of odontogenesis, as well as in nerve fibers that surround the developing tooth germs. At more advanced developmental stages, NGF and TrkA are localized in differentiated cells with secretory capacities such as preameloblasts/ameloblasts secreting enamel matrix and odontoblasts secreting dentine matrix. In contrast, p75NTR expression is absent from these secretory cells and restricted in proliferating cells of the dental epithelium. The temporospatial distribution of NGF and p75NTR in fetal human teeth is similar, but not identical, with that observed previously in the developing rodent teeth, thus indicating that the genetic information is well-conserved during evolution. The expression patterns of NGF, p75NTR, and TrkA during odontogenesis suggest regulatory roles for NGF signaling in proliferation and differentiation of epithelial and mesenchymal cells, as well as in attraction and sprouting of nerve fibers within dental tissues.
Highlights
The present study describes the distribution of nerve growth factor (NGF), p75NTR, and TrkA proteins in the developing human fetal teeth, and confirms that their temporospatial distribution in human dental tissues is very similar with that observed previously in rodents (Yan and Johnson, 1988; Byers et al, 1990; Mitsiadis et al, 1992, 1993; Mitsiadis and Luukko, 1995)
NGF is expressed in the epithelium during the early stages of tooth development, while p75NTR and TrkA are first expressed in the mesenchyme
The expression of NGF, TrkA, and p75NTR in the tooth germ significantly precedes the onset of tooth innervation
Summary
The roles of nerve growth factor (NGF) in the development, survival and maintenance of selected group of neurons of the peripheral and central nervous system have been thoroughly evaluated in the last few decades (Chao, 2003; Lu et al, 2005; Reichardt, 2006; Ichim et al, 2012; Lewis and Carter, 2014). Additional members of the NGF-related family of neurotrophic molecules include brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), neurotrophin-4 (NT-4; known as NT-4/5 or NT-5), and neurotrophin-6 (NT-6; Chao, 2003; Lu et al, 2005; Reichardt, 2006; Lewis and Carter, 2014). Two binding affinities of NTFs to their receptors, one high, the other low, have
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