# Characterization of PDGFR dimer-specific dynamics in the craniofacial mesenchyme

> **NIH NIH K02** · UNIVERSITY OF COLORADO DENVER · 2023 · $125,331

## Abstract

Project Summary
Craniofacial development is a complex morphogenetic process, disruptions in which result in highly
prevalent human birth defects. Signaling through the platelet-derived growth factor receptors (PDGFRs) plays
a critical role in this process in humans and mice. PDGFRalpha and PDGFRBeta have recently been shown to
genetically and physically interact in the craniofacial mesenchyme to form functional heterodimers with unique
signal molecule binding properties and the ability to generate more robust intracellular signaling and mitogenic
responses in vitro than those generated by homodimeric receptor complexes. The aim of this proposal is to
examine the in vivo dynamics of PDGFR dimer-specific formation, as well as the resulting effects on gene
expression and cell activity in the craniofacial mesenchyme. First, PDGFR-bimolecular fluorescence
complementation (BiFC) fragment alleles will be generated containing the N- or C-terminal regions of the
Venus fluorescent protein. Venus expression will be analyzed in craniofacial structures by fluorescence
microscopy to examine the spatiotemporal dynamics of PDGFR homodimer versus heterodimer formation.
Second, the effect of SHP-2 binding to PDGFRalpha on downstream signaling will be determined through genetic
epistasis experiments and, in parallel, BiFC and affinity purification will be employed to selectively purify
PDGFRalpha/Beta heterodimers and identify PDGFR dimer-specific interacting proteins by mass spectrometry.
Finally, RNA-sequencing will be performed to define the transcriptional program induced downstream of
PDGFR dimer-specific activation in the maxillary processes. Additional experiments, technologies and training
opportunities are introduced in this Independent Scientist Award application that significantly extend and
enhance the original research plan and allow for career development. These include cell biology and superresolution
microscopy training to characterize the subcellular localization and internalization dynamics of the
various PDGFR dimers; training in the application of bioinformatics approaches for RNA-sequencing analysis;
and participation in leadership and scientific communication training programs. This training plan will take place
within the School of Dental Medicine at the University of Colorado Anschutz Medical Campus, which has a
strong, well-established research program in craniofacial biology and provides ample opportunities for training
and collaboration. University support includes guaranteed salary support beyond the award period; provision of
funds for post-doctoral fellow recruitment, shared equipment usage, course tuition and travel to scientific
meetings; permission for the candidate to spend essentially full-time conducting research; and participation in
joint lab meetings and working groups designed to facilitate the development of the candidate's research
program. Combined, these activities will contribute towards the goal of establishing a recogn...

## Key facts

- **NIH application ID:** 10576282
- **Project number:** 5K02DE028572-05
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Katherine Ann Fantauzzo
- **Activity code:** K02 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $125,331
- **Award type:** 5
- **Project period:** 2019-04-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10576282

## Citation

> US National Institutes of Health, RePORTER application 10576282, Characterization of PDGFR dimer-specific dynamics in the craniofacial mesenchyme (5K02DE028572-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10576282. Licensed CC0.

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