# Ion channel mediated control of mophogen signaling for craniofacial development in mammals

> **NIH NIH R01** · UNIVERSITY OF COLORADO DENVER · 2021 · $357,186

## Abstract

PROJECT SUMMARY
 Craniofacial reconstruction is required after trauma, tumors, and for craniofacial disorders. Bone grafts and
synthetic scaffolds have resulted in limited success. Bone morphogenetic proteins (BMPs) stimulate the
production of bone and cartilage, and are necessary for tooth development, palate closure and normal
craniofacial development. BMPs are also required for bone repair and can stimulate stem cells to take on
cartilage and bone fate. We recently discovered that ion channels control the secretion of BMP in the fruit fly.
Our hypothesis is that ion channel activity regulates BMP secretion in mammals in a conserved
mechanism. In support of this hypothesis, mice with disrupted potassium channel function have decreased
activation of BMP signaling and similar phenotypes to BMP mutants. If our hypothesis proves correct, electrical
stimuli or small molecules that affect ion channel activity may provide the ability to control release of BMP for
proper bone and tooth development and regeneration. Our long-term goal is to use a novel approach of
manipulating cells to secrete endogenous BMP to encourage craniofacial bone development. The first step
towards this goal is to determine the mechanism by which an ion channel contributes to BMP signaling in
mammals. In this proposal, we use the Kir2.1 potassium (K+) channel to determine the molecular connection
between ion conductivity and BMP signaling in mammals. Humans and mice with mutations in Kir2.1 have
congenital craniofacial defects including cleft palate, dental defects, and micrognathia showing that this
channel plays an essential role in craniofacial development. Aim 1 determines where Kir2.1 acts in the BMP
pathway in mammals using epistasis and rescue experiments. Aim 2 tests the hypothesis that ion channels
regulate BMP secretion in mammals as they do in flies. In other cell types, ion channels influence intracellular
calcium to regulate secretion. In Aim 3, we determine how intracellular calcium influences BMP release. The
proposed experiments will lay a foundation for future studies to harness the potential of ion channels to
stimulate tissue growth and regeneration.

## Key facts

- **NIH application ID:** 10171404
- **Project number:** 5R01DE025311-04
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Emily Bates
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $357,186
- **Award type:** 5
- **Project period:** 2018-06-08 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10171404

## Citation

> US National Institutes of Health, RePORTER application 10171404, Ion channel mediated control of mophogen signaling for craniofacial development in mammals (5R01DE025311-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10171404. Licensed CC0.

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