Expression of neurotrophin receptors during rat tooth development is developmentally regulated, independent of innervation, and suggests functions in the regulation of morphogenesis and innervation

Luukko, Keijo; Moshnyakov, Maxim; Sainio, Kirsi; Saarma, Märt; Sariola, Hannu; Thesleff, Irma

doi:10.1002/(sici)1097-0177(199605)206:1<87::aid-aja8>3.0.co;2-x

Cited by 83 publications

(73 citation statements)

References 68 publications

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“…Truncated TrkB-T1 mediates neurotrophin-evoked calcium signaling in glia cells (31) and plays a direct signaling role in mediating inositol-1,4,5-trisphoshatedependent calcium release. In developing teeth, TrkB-T1, but not TrkB-FL or TrkB-T2, is detected by in situ hybridization (32). In the present study, all types of TrkB were detected in P3 tooth germ epithelia and a dental epithelial cell line.…”

Section: Discussionsupporting

confidence: 42%

Neurotrophic Factor Neurotrophin-4 Regulates Ameloblastin Expression via Full-length TrkB

Yoshizaki

Yamamoto

Yamada

et al. 2008

Journal of Biological Chemistry

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Neurotrophic factors play an important role in the development and maintenance of not only neural but also nonneural tissues. Several neurotrophic factors are expressed in dental tissues, but their role in tooth development is not clear. Here, we report that neurotrophic factor neurotrophin (NT)-4 promotes differentiation of dental epithelial cells and enhances the expression of enamel matrix genes. Dental epithelial cells from 3-day-old mice expressed NT-4 and three variants of TrkB receptors for neurotrophins (full-length TrkB-FL and truncated TrkB-T1 and -T2). Dental epithelial cell line HAT-7 expressed these genes, similar to those in dental epithelial cells. We found that NT-4 reduced HAT-7 cell proliferation and induced the expression of enamel matrix genes, such as ameloblastin (Ambn). Transfection of HAT-7 cells with the TrkB-FL expression construct enhanced the NT-4-mediated induction of Ambn expression. This enhancement was blocked by K252a, an inhibitor for Trk tyrosine kinases. Phosphorylation of ERK1/2, a downstream molecule of TrkB, was induced in HAT-7 cells upon NT-4 treatment. TrkB-FL but not TrkB-T1 transfection increased the phosphorylation level of ERK1/2 in NT-4-treated HAT-7 cells. These results suggest that NT-4 induced Ambn expression via the TrkB-MAPK pathway. The p75 inhibitor TAT-pep5 decreased NT-4-mediated induction of the expression of Ambn, TrkB-FL, and TrkB-T1, suggesting that both high affinity and low affinity neurotrophin receptors were required for NT-4 activity. We found that NT-4-null mice developed a thin enamel layer and had a decrease in Ambn expression. Our results suggest that NT-4 regulates proliferation and differentiation of the dental epithelium and promotes production of the enamel matrix.Mammalian development is a complex and highly orchestrated process that involves intricate cross-talk between growth factors and other regulatory molecules. The interaction between the epithelium and mesenchyme induces specific molecular and cellular changes that lead to organogenesis. These interactions are particularly crucial during the initiation of the development of ectodermal organs, such as teeth, skin, hair, and mammary and prostate glands (1). The oral epithelium provides the initial signaling for neuronal crest-derived ectomesenchyme development, and then both tissues interact during tooth formation. Various transcription factors, growth factors, and extracellular matrices are expressed by enamel matrix-producing ameloblasts during tooth development (2-4). The principal components of the enamel matrix that are synthesized by secretory ameloblasts can be classified into two major categories, amelogenin (Amel) 2 and non-Amel, which includes ameloblastin (Ambn) and enamelin (Enam) (5). Ambn, also known as amelin or sheathlin, is a tooth-specific glycoprotein that represents the most abundant non-Amel enamel matrix protein. We previously created Ambn-null mice, which develop severe enamel hypoplasia in which ameloblasts detached from the matrix, lost cell polarity, resumed ...

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Section: Discussionsupporting

confidence: 42%

Neurotrophic Factor Neurotrophin-4 Regulates Ameloblastin Expression via Full-length TrkB

Yoshizaki

Yamamoto

Yamada

et al. 2008

Journal of Biological Chemistry

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“…The mouse Bmp2-6 cDNAs, which were a kind gift of Dr. Wozney of the Genetics Institute (Cambridge, MA), have been described earlier in Vainio et al (1993) and Aberg et al (1997). In vitro transcription and in situ hybridization were performed as described in Luukko et al (1996). In brief, the cDNA fragments containing plasmids were linearized, and antisense and sense RNA probes were generated using 35 S-labeled UTP (Amersham, Buckinghamshire, U.K.) and appropriate RNA polymerases.…”

Section: In Situ Hybridizationmentioning

confidence: 99%

Histological development and dynamic expression of Bmp2–6 mRNAs in the embryonic and postnatal mousecranial base

et al. 2006

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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. To investigate this, we analyzed the mRNA pattern of expression of Bmp2-6 in the mouse cranial base from E10 to 5 days postnatally using radioactive in situ hybridization. We found that the formation of the mouse cranial base corresponds to that of rat and proceeds in a caudorostral sequence. Moreover, all Bmps studied showed distinct and overlapping developmentally regulated expression domains. Bmp2, Bmp5, and Bmp6 were expressed in the early mesenchymal condensations. Later, Bmp2, Bmp3, Bmp4, and Bmp5 were detected in the perichondrium and in the adjacent mesenchyme. Subsequently, Bmp2 and Bmp6 expressions were confined to hypertrophic chondrocytes, while Bmp3, Bmp4, and Bmp5 were expressed in the osteoblasts of the trabecular bone and bone collar. Interestingly, Bmp3 was uniquely expressed postnatally in the resting zone of the synchondrosis growth center, suggesting a role in the regulation of cranial base growth. These results suggest that Bmp signaling may serve specific and synergistic functions at different key stages of cranial base development and growth. Anat Rec Part A, 288A:1250-1258, 2006. 2006 Key words: bone morphogenetic proteins; skeletogenesis; endochondral bone; hard tissue; growth; synchondrosisThe cranial base, which is located between the brain and the facial bones, forms the floor of the neurocranium and is established by the coordinated development and growth of several skeletal elements. The human midline cranial base is composed of the basioccipital, sphenoid, ethmoid, and frontal bones (Scott, 1958). The cranial base is an important growth center of the head and is believed to play a significant role in the integration of craniofacial development and growth.In contrast to the bones of the cranial vault and the face, which are formed by intramembranous ossification, the midline cranial base bones, like the long bones, the vertebrae, and the ribcage, are formed by endochondral ossification. However,

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“…In situ hybridization on sections was performed as described previously (Luukko et al, 1996). Briefly, 35 S-UTP-labeled Shh, Ihh, and Sox9 antisense and sense cRNA probes were generated by in vitro transcription.…”

Section: Construction Of Probes and In Situ Hybridizationmentioning

confidence: 99%

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

et al. 2005

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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. Of the Hhs, Shh was observed in the foregut epithelium and the notochord, while Sox9 showed broad expression in the loose mesenchyme of the cranial base area during E10 -E11. Subsequently, from E12 onward, all genes were observed in the developing cranial base, and after birth the genes were prominently colocalized in the prehypertrophic chondrocytes of the synchondroses. Collectively, these data suggest that Hh-Sox9 auto-and paracrine signaling interactions may provide a critical mechanism for regulating the patterning of the cranial base as well as for its development and growth.

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Expression of neurotrophin receptors during rat tooth development is developmentally regulated, independent of innervation, and suggests functions in the regulation of morphogenesis and innervation

Cited by 83 publications

References 68 publications

Neurotrophic Factor Neurotrophin-4 Regulates Ameloblastin Expression via Full-length TrkB

Neurotrophic Factor Neurotrophin-4 Regulates Ameloblastin Expression via Full-length TrkB

Histological development and dynamic expression of Bmp2–6 mRNAs in the embryonic and postnatal mousecranial base

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

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