Expression patterns of Sema3F, PlexinA4, -A3, Neuropilin1 and -2 in the postnatal mouse molar suggest roles in tooth innervation and organogenesis.

Objective: Semaphorins form a family of axon wiring molecules but still little is known about their role in tooth formation. A class 3 semaphorin, Semaphorin3F (Sema3F), besides acting as a chemorepellant for different types of axons, controls a variety of non-neuronal developmental processes.

Materials And Methods: Cellular mRNA expression patterns of Sema3F as well as neuropilin 1 (Npn1), neuropilin 2 (Npn2), plexinA3 and plexinA4 receptors were analyzed by sectional in situ hybridization in the mouse molar tooth during postnatal days 0-7.

Developmentally regulated expression of Sema3A chemorepellant in the developing mouse incisor.

Objective: Semaphorin 3A (Sema3A) is an essential chemorepellant controlling peripheral axon pathfinding and patterning, but also serves non-neuronal cellular functions. Incisors of rodent are distinctive from molars as they erupt continuously, have only one root and enamel is present only on the labial side. The aim of this study is to address putative regulatory roles of Sema3A chemorepellant in the development of incisor innervation and formation.

Developmentally regulated expression of intracellular Fgf11-13, hormone-like Fgf15 and canonical Fgf16, -17 and -20 mRNAs in the developing mouse molar tooth.

Objective: To investigate and compare the cellular expression of non-secreted Fgf11-14 and secreted Fgf15-18 and -20 mRNAs during tooth formation.

Materials And Methods: mRNA expression was analyzed from the morphological initiation of the mouse mandibular first molar development to the onset of crown calcification using sectional in situ hybridization.

Results: This study found distinct, differentially regulated expression patterns for the Fgf11-13, -15-17 and -20, in particular in the epithelial-mesenchymal interface, whereas Fgf14 and 18 mRNAs were not detected.

Development of the pioneer sympathetic innervation into the dental pulp of the mouse mandibular first molar.

Objective: Our goal was to study the development of pioneer sympathetic innervation of dental pulp of mouse mandibular first molar.

Design: We used double fluorescent immunohistochemistry with tyrosine hydroxylase (TH) and anti-medium-chain neurofilament (2H3) antibodies to detect sympathetic and sensory nerve fibres. Serial sections of whole teeth from postnatal days (PN) 0-14, trigeminal and sympathetic superior cervical ganglia of PN 15 mice were examined with confocal microscope.

Secondary induction and the development of tooth nerve supply.

During embryogenesis, dental trigeminal axon navigation and patterning in the developing tooth take place in a highly spatio-temporally directed manner that is tightly linked to tooth morphogenesis and cell differentiation. Tooth formation is regulated by sequential and reciprocal tissue interactions between dental epithelium and neural crest-derived ectomesenchymal cells. This odontogenic secondary induction is mediated by signal molecules of different conserved families.

Fgfr2b mediated epithelial-mesenchymal interactions coordinate tooth morphogenesis and dental trigeminal axon patterning.

Dental trigeminal nerve fiber growth and patterning are strictly integrated with tooth morphogenesis, but it is still unknown, how these two developmental processes are coordinated. Here we show that targeted inactivation of the dental epithelium expressed Fgfr2b results in cessation of the mouse mandibular first molar development at the degenerated cap stage and the failure of the trigeminal molar nerve to establish the lingual branch at E13.5 stage while the buccal branch develops properly.

Histological development and dynamic expression of Bmp2-6 mRNAs in the embryonic and postnatal mouse cranial base.

The cranial base is formed by endochondral ossification and is characterized by the presence of the synchondrosis growth centers. The aim of this study was to describe the histological development of the mouse midsagittal cranial base area from embryonic day 10 (E10) to the postnatal age of 2 months. The Bmp family of signaling molecules serves important functions in embryo and bone development and may therefore play a significant role in the early formation of the cranial base.

Developmental expression of Dkk1-3 and Mmp9 and apoptosis in cranial base of mice.

The Dickkopf (Dkk) family and Mmp9 are important for apoptosis and a number of other developmental processes. However, little is known about their roles in the development of cranial base, which is an important structure for coordinated development and growth of the craniofacial skeletons. In order to establish whether and in what way these genes are involved in cranial base development, we examined their expression patterns and cell apoptosis.

Tissue interactions in the regulation of axon pathfinding during tooth morphogenesis.

Like many other organs, the tooth develops as a result of the epithelial-mesenchymal interactions. In addition, the tooth is a well-defined peripheral target organ for sensory trigeminal nerves, which are required for the function and protection of the teeth. Dental trigeminal axon growth and patterning are tightly linked with advancing tooth morphogenesis and cell differentiation.

Developmentally regulated expression of Shh and Ihh in the developing mouse cranial base: comparison with Sox9 expression.

The cranial base, located between the cranial vault and the facial bones, plays an important role in integrated craniofacial development and growth. Transgenic Shh and Sox9-deficient mice show similar defects in cranial base patterning. Therefore, in order to examine potential interactions of Shh, Ihh, another member of the Hh family, and Sox9 during cranial base development and growth, we investigated their cellular mRNA expression domains in the embryonic (E) and early postnatal (PN) cranial base from E10 to PN5 using sectional radioactive 35-S in situ hybridization.

Dynamic expression of Wnt signaling-related Dickkopf1, -2, and -3 mRNAs in the developing mouse tooth.

Wnt signaling is essential for tooth formation. Members of the Dickkopf (Dkk) family modulate the Wnt signaling pathway by binding to the Wnt receptor complex. Comparison of Dkk1, -2, and -3 mRNA expression during mouse tooth formation revealed that all three genes showed distinct spatiotemporally regulated expression patterns.

Coordination of trigeminal axon navigation and patterning with tooth organ formation: epithelial-mesenchymal interactions, and epithelial Wnt4 and Tgfbeta1 regulate semaphorin 3a expression in the dental mesenchyme.

During development, trigeminal nerve fibers navigate and establish their axonal projections to the developing tooth in a highly spatiotemporally controlled manner. By analyzing Sema3a and its receptor Npn1 knockout mouse embryos, we found that Sema3a regulates dental trigeminal axon navigation and patterning, as well as the timing of the first mandibular molar innervation, and that the effects of Sema3a appear to be mediated by Npn1 present in the axons. By performing tissue recombinant experiments and analyzing the effects of signaling molecules, we found that early oral and dental epithelia, which instruct tooth formation, and epithelial Wnt4 induce Sema3a expression in the presumptive dental mesenchyme before the arrival of the first dental nerve fibers.

Expression of ephrin-A ligands and EphA receptors in the developing mouse tooth and its supporting tissues.

Ephrins are cell-membrane-bound ligands for Eph receptor tyrosine kinases and regulate a variety of developmental processes. In order to investigate the potential roles of the ephrin-Eph system in tooth formation, we studied the cellular mRNA expression of Ephrin-A1-A5 and EphA2, EphA3, EphA4, EphA7, and EphA8 receptors during embryonic histomorphogenesis of the mouse first molar (embryonic days 11.5-18.

Glial cell line-derived neurotrophic factor (GDNF) from adult rat tooth serves a distinct population of large-sized trigeminal neurons.

Glial cell line-derived neurotrophic factor (GDNF) mediates trophic effects for specific classes of sensory neurons. The adult tooth pulp is a well-defined target of sensory trigeminal innervation. Here we investigated potential roles of GDNF in the regulation of adult trigeminal neurons and the dental pulp nerve supply of the rat maxillary first molar.

CGRP1 and NK1 receptors in postnatal, developing rat dental tissues.

There is little evidence that neuropeptides such as substance P (SP) and calcitonin gene-related peptide (CGRP) participate in the regulation of tooth development. The aim of this study was to analyse the expression of their respective receptors, neurokinin (NK) 1 and CGRP1 receptor, in postnatal developing rat molars and supporting tissues, thereby localizing the target areas for neuropeptide activity. Mol:WIST rats were killed at 7, 14 and 21 d after birth and upper and lower jaws were processed for immunohistochemistry.

Developmentally regulated expression of Netrin-1 and -3 in the embryonic mouse molar tooth germ.

The Netrins form a small, conserved family of laminin-related signaling proteins regulating axon guidance in the developing nervous system. Here, we analyzed the roles of Netrin-1 and -3 in trigeminal axon guidance to the first lower molar of the embryonic mouse. Netrin-1 showed a restricted epithelial expression domain buccal to the tooth germ, toward which the pioneer tooth axons initially appear to navigate.

Identification of a novel putative signaling center, the tertiary enamel knot in the postnatal mouse molar tooth.

The final shape of the molar tooth crown is thought to be regulated by the transient epithelial signaling centers in the cusp tips, the secondary enamel knots (SEKs), which are believed to disappear after initiation of the cusp growth. We investigated the developmental fate of the signaling center using the recently characterized Slit1 enamel knot marker as a lineage tracer during morphogenesis of the first molar and crown calcification in the mouse. In situ hybridization analysis showed that after Fgf4 downregulation in the SEK, Slit1 expression persisted in the deep compartment of the knot.