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LGR4 is required for sequential molar development.

Yukiko Yamakami¹, Koki Kohashi¹, Kazunori Oyama¹

¹Laboratory of Molecular Biology, Department of Molecular and Cell Biology, Graduate School of Agricultural Science, Tohoku University, 1-1 Tsutsumidori-Amamiyamachi, Aoba-ku, Sendai, Miyagi, 981-8555 Japan.

Biochemistry and Biophysics Reports

|September 29, 2017

Summary

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Leucine-rich repeat-containing G protein coupled receptor 4 (LGR4) is crucial for sequential molar development in mice. Loss of LGR4 in dental epithelium disrupts SOX2+ cell maintenance, leading to third molar defects.

Area of Science:

Developmental Biology
Molecular Biology
Oral Biology

Background:

Tooth development involves complex cell signaling between epithelial and mesenchymal cells.
Leucine-rich repeat-containing G protein coupled receptor 4 (LGR4) is vital for organogenesis and stem cell maintenance.
LGR4, a receptor for R-spondins, is expressed in various epithelial tissues.

Purpose of the Study:

To investigate the role of LGR4 in the sequential development of mouse molars.
To determine the cellular and molecular mechanisms underlying LGR4's function in tooth germ development.

Main Methods:

Analysis of LGR4 expression in dental epithelium using SOX2+ cell markers.
Generation and analysis of keratinocyte-specific Lgr4-deficient mice (Lgr4-/-).

Keywords:

Dental epithelial stem cell LGR4 Molar development SOX2

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Assessment of molar development, cell proliferation (SOX2+ cells), differentiation, and Wnt/β-catenin signaling (LEF1 expression) at various postnatal stages.

Main Results:

LGR4 is expressed in SOX2+ cells in developing second and third molars (M2 and M3).
Lgr4-/- mice exhibited significant M3 developmental defects, including absence or dwarfing by postnatal day 14.
Loss of LGR4 led to down-regulated Wnt/β-catenin signaling, reduced SOX2+ cell proliferation, and abnormal differentiation in M3 dental epithelium.

Conclusions:

LGR4 is essential for the sequential development of molars in mice.
LGR4 maintains SOX2+ stem cells in the dental epithelium, which are critical for normal molar formation.
Disruption of LGR4 function impairs Wnt/β-catenin signaling and cellular processes necessary for tooth development.