# The Role of FAM20B-Catalyzed Proteoglycans in Tooth Development

> **NIH NIH K02** · TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR · 2022 · $149,246

## Abstract

Project summary/Abstract
The candidate received his first R01 grant in April 2017. At this critical point of his career, he needs at least
75% of protected time on research to develop into the type of scientist he wants to become and secure NIH
funding as an independent scientist after this R01 grant is completed. The R01 project is summarized below.
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. The candidate’s 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. Their 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. Their 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 the candidate to form his 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. He proposes three specific aims to test this
hypothesis: (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. (2) To determine whether FAM20B-catalyzed proteoglycans regulate tooth renewal by
mediating stem cell renewal in the dental epithelium, and (3) To identify the proteoglycans responsible for
the supernumerary tooth formation. The completion of this study will advance the understanding about the
molecular mechanism underlying supernumerary tooth formation and help in laying the groundwork for tooth
regeneration. As FAM20B and proteoglycans are extensively present in many tissues, the knowledge
gained from this study may shed light on the proteoglycan-mediated signaling in other tissues.

## Key facts

- **NIH application ID:** 10471850
- **Project number:** 5K02DE028345-05
- **Recipient organization:** TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR
- **Principal Investigator:** XIAOFANG WANG
- **Activity code:** K02 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $149,246
- **Award type:** 5
- **Project period:** 2018-09-18 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10471850

## Citation

> US National Institutes of Health, RePORTER application 10471850, The Role of FAM20B-Catalyzed Proteoglycans in Tooth Development (5K02DE028345-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10471850. Licensed CC0.

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