# Ameloblast-specific mineral ribbon attachment/elongation complex in enamel formation

> **NIH NIH R00** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2024 · $249,000

## Abstract

PROJECT SUMMARY/ABSTRACT
Single allelic defects in BM-associated genes COL 17 A 1, LAMA3, and LAMB3 cause autosomal dominant
amelogenesis imperfecta in humans. They are strongly expressed in secretory ameloblasts, and localize along
the enamel mineralization front, where no BM structure is observed. These findings lead to the hypothesis that
the proteins of the basement membrane attachment complex are critical components of the ameloblastspecific
mineral ribbon attachment/elongation complex that extends and orients enamel ribbons at the
mineralization front during the secretory stage of amelogenesis.
Three specific aims (SA) are proposed. SA1: Identify the critical components of the ameloblast-specific mineral
ribbon attachment/elongation complex in wild-type 0,/VT) mice. Potential components of this complex have been
localized at the Tomes' process during the K99 phase. The localization of BM-associated components at the
electron microscopy level will be defined, and protein interactions among them will be further explored during
the R00 phase. SA2: Determine the function of LAMA3 during enamel formation by conditionally knocking out
Lama3 expression in ameloblasts. The Amelx-iCre;Lama3nm mice have been validate and show hypoplastic
enamel. I will further examine the molecular changes and use focused ion beam scanning electron microscopy
to characterize the ultrastructural changes in enamel formation in Amelx-iCre;Lama3fltfl mice. SA3: Generate a
Co/17a1 conditional knockout mouse model and determine the function of type XVII collagen in enamel formation.
A Co/17a1fl mouse has been generated and validated at multiple levels. Preliminary results showed that the
enamel phenotype of Amelx-iCre;Co/17a1fl1fl mice was comparable to those of the WT. I will complete the
characterizations of the Amelx-iCre;Co/17a1fl1fl mice. In addition, I will investigate the roles of Co/17a1 in
presecretory ameloblasts in Krt14-Cre-ERr2;Co/17a1fltfl mice. I will induce the epithelium-specific removal of
Co/17a1 in the Krt14-Cre-ERr2;Co/17a1fltfl mice and harvest the incisors later for molecular and ultrastructural
characterizations. The completion of this proposal will advance our understanding of enamel formation, shed
light on the treatment options of amelogenesis imperfecta, and provide insights for enamel biomimetics. The
Co/17a1fl mouse will also become a critical tool for studies of type XVII collagen in other organs and tissues.
My career goal is to study the regulations of biomineralization, particularly in enamel and dentin formation. During
the K99 phase, I have completed a series of scientific training and career development activities. I will transition
to a tenure-track assistant professor in the R00 phase. I will establish a robust independent laboratory and
continue my investigations in the field of tooth development and biomineralization.

## Key facts

- **NIH application ID:** 11017291
- **Project number:** 4R00DE030858-03
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** TIAN LIANG
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $249,000
- **Award type:** 4N
- **Project period:** 2024-07-01 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11017291

## Citation

> US National Institutes of Health, RePORTER application 11017291, Ameloblast-specific mineral ribbon attachment/elongation complex in enamel formation (4R00DE030858-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/11017291. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*