Semaphorin 3A controls timing and patterning of the dental pulp innervation

Moe, Kyaw Kyaw; Sijaona, Angelina; Shrestha, Anjana; Kettunen, Päivi; Taniguchi, Masahiko; Luukko, Keijo

doi:10.1016/j.diff.2012.09.003

Cited by 22 publications

(34 citation statements)

References 43 publications

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“…For example, dynamic expression patterns of NGF mRNA during the embryonic and postnatal development of the incisor and molar teeth, correlate with pivotal phases of tooth innervation. These data suggest that NGF may control dental axon guidance, and target field innervation, 31,34,25 in addition to its functions in neuronal survival. 35,36,35,37 Locally expressed SEMA3A regulates tooth innervation…”

Section: The Adult Tooth Nerve Supply and Its Functionsmentioning

confidence: 98%

“…26,45 However, an abnormal, elevated number of axons and their arborization, is observed in the incisor periodontium, particularly at the labial side. 26 The finding that some degree of correction occurred in the dental nerve patterning of Sema3A ¡/¡ molars 25 suggests that other neuro-regulatory molecules may compensate for the lack of SEMA3A signaling. For example, the expression of NGF and GDNF (that exert positive influences on axon growth and tooth target innervation), and their receptors, are unaltered in the trigeminal ganglion during various stages of tooth innervation in Sema3A-mutant teeth.…”

Section: The Adult Tooth Nerve Supply and Its Functionsmentioning

confidence: 99%

“…23,25,26 The dental pulp of Sema3A ¡/¡ molars are also prematurely innervated, with axons exhibiting abnormal patterning and fasciculation, in particular within the enlarged and defective subodontoblastic nerve plexus. 25 In contrast, the innervation of the dental pulp in Sema3A ¡/¡ incisors appears normal, reflecting the finding that Sema3A is largely nonexistent in the postnatal incisor pulp. 26,45 However, an abnormal, elevated number of axons and their arborization, is observed in the incisor periodontium, particularly at the labial side.…”

Section: The Adult Tooth Nerve Supply and Its Functionsmentioning

confidence: 99%

“…7,23,26,45 Analyses of Sema3A-deficient transgenic mice confirmed that SEMA3A is a critical regulator of tooth innervation, that is serially exploited at critical embryonic and postnatal stages of tooth innervation. 23,25,26 In both Sema3A-deficient incisor and molar tooth germs, pioneer axons reach the tooth germ prematurely and show apparent disturbances in nerve patterning and fasciculation. Although dental mesenchymal target areas become innervated, nerve fibers frequently overshoot their targets, to enter abnormal ectopic locations within mesenchymal exclusion areas, which would suggest a failure of the surrounding repulsion mechanisms (Fig.…”

Section: The Adult Tooth Nerve Supply and Its Functionsmentioning

confidence: 99%

“…32,23,13,25,26 the mesenchymal dental follicle target area, which ultimately forms the periodontium (during root formation and tooth eruption) that attaches roots to alveolar bone. 10,13,23,25,26 Of note, although the nerves already surround the developing tooth organ during embryonic stages, axons will only grow into the mesenchymal dental pulp post-natally. Typically this occurs after a delay of about 10 days (from the first encounter of axons with the tooth target), on postnatal day 3-4.…”

Section: The Adult Tooth Nerve Supply and Its Functionsmentioning

confidence: 99%

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Integration of tooth morphogenesis and innervation by local tissue interactions, signaling networks, and semaphorin 3A

Luukko

Kettunen

2016

Cell Adhesion & Migration

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The tooth, like many other organs, develops from both epithelial and mesenchymal tissues, and has proven to be a valuable tool with which to investigate organ formation and peripheral innervation. Tooth formation is regulated by local epithelial-mesenchymal tissue interactions, and is closely integrated with stereotypic dental nerve navigation and patterning. Recent analyses of the function and regulation of semaphorin 3A (SEMA3A) have shed light on the regulatory mechanisms that coordinate organogenesis and innervation at the tissue and molecular levels. In the tooth, SEM3A acts as a developmentally regulated secretory chemo-repellent, that controls tooth innervation during embryonic and postnatal development. The tooth germ governs its own innervation by a combination of local tissue interactions and SEMA3A expression. SEMA3A signaling, in turn, is controlled by a number of conserved signaling effectors, including TGF-b superfamily members, FGF, and WNT; all function in embryo and organ development, and are essential for tooth histo-morphogenesis. Thus, SEMA3A driven axon guidance is integrated into key odontogenic signaling networks, establishing this protein as a critical molecular tether between 2 distinct developmental processes (morphogenesis and sensory innervation), both of which are required to obtain a functional tooth.

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Section: The Adult Tooth Nerve Supply and Its Functionsmentioning

confidence: 98%

Section: The Adult Tooth Nerve Supply and Its Functionsmentioning

confidence: 99%

Section: The Adult Tooth Nerve Supply and Its Functionsmentioning

confidence: 99%

Section: The Adult Tooth Nerve Supply and Its Functionsmentioning

confidence: 99%

Section: The Adult Tooth Nerve Supply and Its Functionsmentioning

confidence: 99%

See 3 more Smart Citations

Integration of tooth morphogenesis and innervation by local tissue interactions, signaling networks, and semaphorin 3A

Luukko

Kettunen

2016

Cell Adhesion & Migration

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Expression of new genes in vertebrate tooth development and p63 signaling

Rostampour

Appelt

Abid

et al. 2019

Developmental Dynamics

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Background p63 is an evolutionarily ancient transcription factor essential to vertebrate tooth development. Our recent gene expression screen comparing wild‐type and “toothless” p63−/− mouse embryos implicated in tooth development several new genes that we hypothesized act downstream of p63 in dental epithelium, where p63 is also expressed. Results Via in situ hybridization and immunohistochemistry, we probed mouse embryos (embryonic days 10.5‐14.5) and spotted gar fish embryos (14 days postfertilization) for these newly linked genes, Cbln1, Cldn23, Fermt1, Krt15, Pltp and Prss8, which were expressed in mouse and gar dental epithelium. Loss of p63 altered expression levels but not domains. Expression was comparable between murine upper and lower tooth organs, implying conserved gene functions in maxillary and mandibular dentitions. Our meta‐analysis of gene expression databases supported that these genes act within a p63‐driven gene regulatory network important to tooth development in mammals and more evolutionary ancient vertebrates (fish, amphibians). Conclusions Cbln1, Cldn23, Fermt1, Krt15, Pltp, and Prss8 were expressed in mouse and fish dental epithelium at placode, bud, and/or cap stages. We theorize that these genes participate in cell‐cell adhesion, cell polarity, and extracellular matrix signaling to support dental epithelium integrity, folding, and epithelial‐mesenchymal cross talk during tooth development.

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Semaphorin 3A receptor inhibitor as a novel therapeutic to promote innervation of bioengineered teeth

Kuchler‐Bopp

Bagnard

Van‐Der‐Heyden

et al. 2018

J Tissue Eng Regen Med

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The sensory innervation of the dental pulp is essential for tooth function and protection. It is mediated by axons originating from the trigeminal ganglia and is spatio-temporally regulated. We have previously shown that the innervation of bioengineered teeth can be achieved only under immunosuppressive conditions. The aim of this study was to develop a model to determine the role of Semaphorin 3A (Sema3A) in the innervation of bioengineered teeth. We first analysed innervation of the dental pulp of mandibular first molars in newborn (postnatal day 0: PN0) mice deficient for Sema3A (Sema3A ), a strong inhibitor of axon growth. While at PN0, axons detected by immunostaining for peripherin and NF200 were restricted to the peridental mesenchyme in Sema3A mice, they entered the dental pulp in Sema3A mice. Then, we have implanted cultured teeth obtained from embryonic day-14 (E14) molar germs of Sema3A mice together with trigeminal ganglia. The dental pulps of E14 cultured and implanted Sema3A teeth were innervated, whereas the axons did not enter the pulp of E14 Sema3A cultured and implanted teeth. A "Membrane Targeting Peptide NRP1," suppressing the inhibitory effect of Sema3A, has been previously identified. The injection of this peptide at the site of implantation allowed the innervation of the dental pulp of bioengineered teeth obtained from E14 dental dissociated mesenchymal and epithelial cells reassociations of ICR mice. In conclusion, these data show that inhibition of only one axon repellent molecule, Sema3A, allows for pulp innervation of bioengineered teeth.

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Semaphorin 3A controls timing and patterning of the dental pulp innervation

Cited by 22 publications

References 43 publications

Integration of tooth morphogenesis and innervation by local tissue interactions, signaling networks, and semaphorin 3A

Integration of tooth morphogenesis and innervation by local tissue interactions, signaling networks, and semaphorin 3A

Expression of new genes in vertebrate tooth development and p63 signaling

Semaphorin 3A receptor inhibitor as a novel therapeutic to promote innervation of bioengineered teeth

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