Targeted p120-catenin ablation disrupts dental enamel development

John D Bartlett; Justine M Dobeck; Coralee E Tye; Mirna Perez-Moreno; Nicole Stokes; Albert B Reynolds; Elaine Fuchs; Ziedonis Skobe

doi:10.1371/journal.pone.0012703

Targeted p120-catenin ablation disrupts dental enamel development

John D Bartlett, Justine M Dobeck, Coralee E Tye, Mirna Perez-Moreno, Nicole Stokes, Albert B Reynolds, Elaine Fuchs, Ziedonis Skobe

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Abstract

Dental enamel development occurs in stages. The ameloblast cell layer is adjacent to, and is responsible for, enamel formation. When rodent pre-ameloblasts become tall columnar secretory-stage ameloblasts, they secrete enamel matrix proteins, and the ameloblasts start moving in rows that slide by one another. This movement is necessary to form the characteristic decussating enamel prism pattern. Thus, a dynamic system of intercellular interactions is required for proper enamel development. Cadherins are components of the adherens junction (AJ), and they span the cell membrane to mediate attachment to adjacent cells. p120 stabilizes cadherins by preventing their internalization and degradation. So, we asked if p120-mediated cadherin stability is important for dental enamel formation. Targeted p120 ablation in the mouse enamel organ had a striking effect. Secretory stage ameloblasts detached from surrounding tissues, lost polarity, flattened, and ameloblast E- and N-cadherin expression became undetectable by immunostaining. The enamel itself was poorly mineralized and appeared to be composed of a thin layer of merged spheres that abraded from the tooth. Significantly, p120 mosaic mouse teeth were capable of forming normal enamel demonstrating that the enamel defects were not a secondary effect of p120 ablation. Surprisingly, blood-filled sinusoids developed in random locations around the developing teeth. This has not been observed in other p120-ablated tissues and may be due to altered p120-mediated cell signaling. These data reveal a critical role for p120 in tooth and dental enamel development and are consistent with p120 directing the attachment and detachment of the secretory stage ameloblasts as they move in rows.

Original language	English
Article number	e12703
Journal	PloS one
Volume	5
Issue number	9
Pages (from-to)	1-11
ISSN	1932-6203
DOIs	https://doi.org/10.1371/journal.pone.0012703
Publication status	Published - 2010
Externally published	Yes

Keywords

Ameloblasts
Animals
Cadherins
Catenins
Dental Enamel
Gene Expression Regulation, Developmental
Gene Targeting
Mice
Mice, Inbred C57BL
Mice, Knockout
Tooth
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

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title = "Targeted p120-catenin ablation disrupts dental enamel development",

abstract = "Dental enamel development occurs in stages. The ameloblast cell layer is adjacent to, and is responsible for, enamel formation. When rodent pre-ameloblasts become tall columnar secretory-stage ameloblasts, they secrete enamel matrix proteins, and the ameloblasts start moving in rows that slide by one another. This movement is necessary to form the characteristic decussating enamel prism pattern. Thus, a dynamic system of intercellular interactions is required for proper enamel development. Cadherins are components of the adherens junction (AJ), and they span the cell membrane to mediate attachment to adjacent cells. p120 stabilizes cadherins by preventing their internalization and degradation. So, we asked if p120-mediated cadherin stability is important for dental enamel formation. Targeted p120 ablation in the mouse enamel organ had a striking effect. Secretory stage ameloblasts detached from surrounding tissues, lost polarity, flattened, and ameloblast E- and N-cadherin expression became undetectable by immunostaining. The enamel itself was poorly mineralized and appeared to be composed of a thin layer of merged spheres that abraded from the tooth. Significantly, p120 mosaic mouse teeth were capable of forming normal enamel demonstrating that the enamel defects were not a secondary effect of p120 ablation. Surprisingly, blood-filled sinusoids developed in random locations around the developing teeth. This has not been observed in other p120-ablated tissues and may be due to altered p120-mediated cell signaling. These data reveal a critical role for p120 in tooth and dental enamel development and are consistent with p120 directing the attachment and detachment of the secretory stage ameloblasts as they move in rows.",

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author = "Bartlett, {John D} and Dobeck, {Justine M} and Tye, {Coralee E} and Mirna Perez-Moreno and Nicole Stokes and Reynolds, {Albert B} and Elaine Fuchs and Ziedonis Skobe",

year = "2010",

doi = "10.1371/journal.pone.0012703",

language = "English",

volume = "5",

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T1 - Targeted p120-catenin ablation disrupts dental enamel development

AU - Bartlett, John D

AU - Dobeck, Justine M

AU - Tye, Coralee E

AU - Perez-Moreno, Mirna

AU - Stokes, Nicole

AU - Reynolds, Albert B

AU - Fuchs, Elaine

AU - Skobe, Ziedonis

PY - 2010

Y1 - 2010

N2 - Dental enamel development occurs in stages. The ameloblast cell layer is adjacent to, and is responsible for, enamel formation. When rodent pre-ameloblasts become tall columnar secretory-stage ameloblasts, they secrete enamel matrix proteins, and the ameloblasts start moving in rows that slide by one another. This movement is necessary to form the characteristic decussating enamel prism pattern. Thus, a dynamic system of intercellular interactions is required for proper enamel development. Cadherins are components of the adherens junction (AJ), and they span the cell membrane to mediate attachment to adjacent cells. p120 stabilizes cadherins by preventing their internalization and degradation. So, we asked if p120-mediated cadherin stability is important for dental enamel formation. Targeted p120 ablation in the mouse enamel organ had a striking effect. Secretory stage ameloblasts detached from surrounding tissues, lost polarity, flattened, and ameloblast E- and N-cadherin expression became undetectable by immunostaining. The enamel itself was poorly mineralized and appeared to be composed of a thin layer of merged spheres that abraded from the tooth. Significantly, p120 mosaic mouse teeth were capable of forming normal enamel demonstrating that the enamel defects were not a secondary effect of p120 ablation. Surprisingly, blood-filled sinusoids developed in random locations around the developing teeth. This has not been observed in other p120-ablated tissues and may be due to altered p120-mediated cell signaling. These data reveal a critical role for p120 in tooth and dental enamel development and are consistent with p120 directing the attachment and detachment of the secretory stage ameloblasts as they move in rows.

AB - Dental enamel development occurs in stages. The ameloblast cell layer is adjacent to, and is responsible for, enamel formation. When rodent pre-ameloblasts become tall columnar secretory-stage ameloblasts, they secrete enamel matrix proteins, and the ameloblasts start moving in rows that slide by one another. This movement is necessary to form the characteristic decussating enamel prism pattern. Thus, a dynamic system of intercellular interactions is required for proper enamel development. Cadherins are components of the adherens junction (AJ), and they span the cell membrane to mediate attachment to adjacent cells. p120 stabilizes cadherins by preventing their internalization and degradation. So, we asked if p120-mediated cadherin stability is important for dental enamel formation. Targeted p120 ablation in the mouse enamel organ had a striking effect. Secretory stage ameloblasts detached from surrounding tissues, lost polarity, flattened, and ameloblast E- and N-cadherin expression became undetectable by immunostaining. The enamel itself was poorly mineralized and appeared to be composed of a thin layer of merged spheres that abraded from the tooth. Significantly, p120 mosaic mouse teeth were capable of forming normal enamel demonstrating that the enamel defects were not a secondary effect of p120 ablation. Surprisingly, blood-filled sinusoids developed in random locations around the developing teeth. This has not been observed in other p120-ablated tissues and may be due to altered p120-mediated cell signaling. These data reveal a critical role for p120 in tooth and dental enamel development and are consistent with p120 directing the attachment and detachment of the secretory stage ameloblasts as they move in rows.

KW - Ameloblasts

KW - Animals

KW - Cadherins

KW - Catenins

KW - Dental Enamel

KW - Gene Expression Regulation, Developmental

KW - Gene Targeting

KW - Mice

KW - Mice, Inbred C57BL

KW - Mice, Knockout

KW - Tooth

KW - Journal Article

KW - Research Support, N.I.H., Extramural

KW - Research Support, Non-U.S. Gov't

U2 - 10.1371/journal.pone.0012703

DO - 10.1371/journal.pone.0012703

M3 - Journal article

C2 - 20862276

SN - 1932-6203

VL - 5

SP - 1

EP - 11

JO - PLoS Computational Biology

JF - PLoS Computational Biology

IS - 9

M1 - e12703

ER -

Targeted p120-catenin ablation disrupts dental enamel development

Abstract

Keywords

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