Role of Hertwig's epithelial root sheath cells in tooth root development

Hertwig’s epithelial root sheath (HERS) is important for tooth root formation, but the molecular basis for the signaling of root development remains uncertain. We hypothesized that Sonic hedgehog (Shh) signaling is involved in the HERS function, because it mediates epithelial-mesenchymal interactions during embryonic odontogenesis. We examined the gene expression patterns of Shh signaling in murine developing molar roots. Shh and Patched2 transcripts were identified in the HERS, whereas Patched1, Smoothened, and Gli1 were expressed in the proliferative dental mesenchyme in addition to the HERS. To confirm whether Shh signaling physiologically functions in vivo, we analyzed mesenchymal dysplasia ( mes) mice carrying an abnormal C-terminus of the PATCHED1 protein. In the mutant, cell proliferation was repressed around the HERS at 1 wk. Moreover, the molar eruption was disturbed, and all roots were shorter than those in control littermates at 4 wks. These results indicate that Shh signaling is important in tooth root development. Abbreviations used: BrdU, 5-bromo-2′-deoxyuridine; HERS, Hertwig’s epithelial root sheath; NFI-C/CTF, nuclear factor Ic/CAAT box transcription factor; PCNA, proliferating cell nuclear antigen; Ptc, patched; Shh, sonic hedgehog; Smo, smoothened.

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Cell dynamics in Hertwig's epithelial root sheath are regulated by β‐catenin activity during tooth root development

Journal of Cellular Physiology ◽

10.1002/jcp.30243 ◽

2020 ◽

Author(s):

Siqin Yang ◽

Hwajung Choi ◽

Tak‐Heun Kim ◽

Ju‐Kyung Jeong ◽

Yudong Liu ◽

...

Keyword(s):

Root Development ◽

Tooth Root ◽

Cell Dynamics ◽

Hertwig’S Epithelial Root Sheath ◽

Root Sheath

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BMP4 signaling regulates formation of Hertwig’s epithelial root sheath during tooth root development

Cell and Tissue Research ◽

10.1007/s00441-008-0655-z ◽

2008 ◽

Vol 333 (3) ◽

pp. 503-509 ◽

Cited By ~ 42

Author(s):

Akihiro Hosoya ◽

Ji-Youn Kim ◽

Sung-Won Cho ◽

Han-Sung Jung

Keyword(s):

Root Development ◽

Tooth Root ◽

Hertwig’S Epithelial Root Sheath ◽

Root Sheath

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Immortalized Hertwig's epithelial root sheath cell line works as model for epithelial–mesenchymal interaction during tooth root formation

Journal of Cellular Physiology ◽

10.1002/jcp.29174 ◽

2019 ◽

Vol 235 (3) ◽

pp. 2698-2709 ◽

Cited By ~ 1

Author(s):

Sicheng Zhang ◽

Xuebing Li ◽

Shikai Wang ◽

Yan Yang ◽

Weihua Guo ◽

...

Keyword(s):

Cell Line ◽

Root Formation ◽

Tooth Root ◽

Sheath Cell ◽

Hertwig’S Epithelial Root Sheath ◽

Root Sheath

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Occurrence of actinlike microfilaments in the outer root sheath cells of the hair follicle: a possible role of a cytoskeleton

Journal of Ultrastructure Research ◽

10.1016/s0022-5320(83)90108-9 ◽

1983 ◽

Vol 85 (2) ◽

pp. 219-227 ◽

Cited By ~ 2

Author(s):

Sadao Sugiyama ◽

Makoto Takahashi ◽

Seiji Furuya

Keyword(s):

Hair Follicle ◽

Outer Root Sheath ◽

Root Sheath ◽

Outer Root Sheath Cells ◽

Sheath Cells

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The Impact of the Eda Pathway on Tooth Root Development

Journal of Dental Research ◽

10.1177/0022034517725692 ◽

2017 ◽

Vol 96 (11) ◽

pp. 1290-1297 ◽

Cited By ~ 7

Author(s):

J.M. Fons Romero ◽

H. Star ◽

R. Lav ◽

S. Watkins ◽

M. Harrison ◽

...

Keyword(s):

Root Development ◽

Tooth Development ◽

Mouse Development ◽

Direct Role ◽

Root Sheath ◽

Crown Shape ◽

High Incidence ◽

Tooth Number ◽

The Impact

The Eda pathway ( Eda, Edar, Edaradd) plays an important role in tooth development, determining tooth number, crown shape, and enamel formation. Here we show that the Eda pathway also plays a key role in root development. Edar (the receptor) is expressed in Hertwig’s epithelial root sheath (HERS) during root development, with mutant mice showing a high incidence of taurodontism: large pulp chambers lacking or showing delayed bifurcation or trifurcation of the roots. The mouse upper second molars in the Eda pathway mutants show the highest incidence of taurodontism, this enhanced susceptibility being matched in human patients with mutations in EDA-A1. These taurodont teeth form due to defects in the direction of extension of the HERS from the crown, associated with a more extensive area of proliferation of the neighboring root mesenchyme. In those teeth where the angle at which the HERS extends from the crown is very wide and therefore more vertical, the mutant HERSs fail to reach toward the center of the tooth in the normal furcation region, and taurodont teeth are created. The phenotype is variable, however, with milder changes in angle and proliferation leading to normal or delayed furcation. This is the first analysis of the role of Eda in the root, showing a direct role for this pathway during postnatal mouse development, and it suggests that changes in proliferation and angle of HERS may underlie taurodontism in a range of syndromes.

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