# The Role of FAM20B-catalyzed Proteoglycans in Tooth Development

> **NIH NIH R01** · TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR · 2021 · $352,688

## Abstract

Project summary/Abstract
Supernumerary teeth can cause a broad range of dental complications. As extra teeth are formed on
existing dentition, unraveling the molecular mechanism of supernumerary tooth formation will not only help
develop the therapeutic strategy for this disease but also provide insights into tooth regeneration. Despite
the significant progress in understanding the regulatory role of morphogens, growth factors, and
transcriptional factors in supernumerary tooth formation, little is known about the role of extracellular
components such as proteoglycans in this pathological process. Our recent studies show that inactivation
of dental epithelial Fam20B, a newly discovered xylose kinase essential for glycosaminoglycan (GAG)
assembly, leads to supernumerary incisors in mice. Our pilot study reveals that GAG deficiency in the
dental epithelium leads to ectopic activation of WNT signaling, and that an ectopic Sox2 expression is
located in the same area, which normally should disappear from this site after E14.5. Our in vitro study
shows that GAGs on certain FAM20B-catalyzed proteoglycans suppress WNT signaling but facilitate Wise-
mediated inhibition on WNT. Conversely, administering WNT inhibitor to the mutant embryos rescued the
tooth phenotype in some cases. These data led us to form our central hypothesis that certain FAM20B-
catalyzed proteoglycans regulate tooth renewal by mediating the stem cell renewal via negative regulation
on WNT signaling in the dental epithelium. To test this hypothesis, we propose the following three specific
aims: (1) To determine if FAM20B-catalyzed proteoglycans mediate tooth renewal via negative regulation
on WNT signaling, and if GAG-mediated Wise inhibition on WNT underlies the supernumerary tooth
formation. We will perform "rescue" experiments by overexpressing DKK1 or Wise in the dental epithelium
to inhibit the overactivated WNT signaling in K14Cre/+;Fam20Bfl/fl mice. (2) To determine whether FAM20B-
catalyzed proteoglycans regulate tooth renewal by mediating the stem cell renewal in the dental epithelium.
We will perform lineage tracing and inducible knockout experiments to determine the role of stem cell
renewal in GAG deficiency-caused supernumerary teeth, and if the FAM20B-catalyzed PGs mediate stem
cell renewal in the dental epithelium in a cell-autonomous manner. (3) To identify the FAM20B-catalyzed
proteoglycans responsible for the supernumerary tooth formation. We will determine the expression pattern
of FAM20B-catalyzed proteoglycans in tooth and identify those negatively regulating WNT signaling. The
biological function of candidate proteoglycans will be determined by gene knockdown and organ culture
methods. The completion of this study will advance our understanding about the molecular mechanism
underlying supernumerary tooth formation and help in laying the groundwork for tooth regeneration. As
FAM20B and proteoglycans are extensively expressed in many tissues, the knowledge gained fr...

## Key facts

- **NIH application ID:** 10129344
- **Project number:** 5R01DE026461-05
- **Recipient organization:** TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR
- **Principal Investigator:** XIAOFANG WANG
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $352,688
- **Award type:** 5
- **Project period:** 2017-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10129344

## Citation

> US National Institutes of Health, RePORTER application 10129344, The Role of FAM20B-catalyzed Proteoglycans in Tooth Development (5R01DE026461-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10129344. Licensed CC0.

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