# Prolonger progenitor maintenance sculpts the upper face

> **NIH NIH R00** · CINCINNATI CHILDRENS HOSP MED CTR · 2020 · $247,165

## Abstract

Project Summary
Prolonged Progenitor Maintenance Sculpts the Upper Face
Though dozens of genes are known to participate in shaping the facial skeleton, how facial skeletal precursors
are differentially allocated into cartilage versus bone fates in different parts of the face remains poorly
understood. Dr. Mork's postdoctoral work in Dr. Gage Crump's lab at USC offers a new perspective on how the
vertebrate skull is built, where prolonged maintenance of skeletal progenitors appears to underlie the increased
proportion of directly-ossifying dermal bone relative to cartilage in the upper versus the lower face. Importantly
for public health, many common craniofacial birth defects affecting various parts of the skull, including
craniosynostosis, cleft palate, and middle ear bone abnormalities, could potentially be explained by precocious
differentiation of skeletal progenitors. The aims outlined in this proposal take genetic and developmental
approaches in zebrafish and mouse models, combined with sophisticated live-imaging and genome-wide
expression analyses, to substantiate this new model of facial patterning. The proposed experiments will build
from her extensive preliminary data to test the hypothesis that two novel targets of the key differentiation-
suppressing Jagged-Notch pathway – Fibroblast Growth Factor 20 (Aim 1) and Nuclear Receptor 2f genes
(Aims 2 & 3) – actively maintain cells in a progenitor state in the upper face of the developing embryo, thereby
preserving dermal bone precursors at the expense of cartilage differentiation in the upper facial skeleton. Aims
1 & 3 will be initiated under the mentorship of Drs. Crump and Chai and completed during the R00 period,
whereas Aim 2 is farther along and will be completed before the end of the K99 phase.
This project has been designed to facilitate Dr. Mork's career goal of obtaining a position as a tenure-track
Assistant Professor at a top-tier academic research institution. She plans to develop an independent research
program relying on state-of-the-art genetic and imaging methods in both zebrafish and mouse models to
address unresolved questions in craniofacial developmental biology with clear relevance for human health.
During the K99 phase, she will benefit from continued mentorship in zebrafish development by Dr. Crump,
crucial training in mouse craniofacial biology from her co-mentor Dr. Yang Chai, and additional career and
scientific guidance at regularly scheduled meetings with her full Advisory Committee. Additional career
development activities at USC, such as grant-writing and mentorship workshops, will prepare Dr. Mork for the
transition to an independent faculty position during the R00 phase. As USC hosts one of the most experienced
and thriving communities of craniofacial and skeletal biologists in the country, there are few better places that
she could acquire the training, resources, and network of collaborators needed to establish herself as an
independent investigator in cr...

## Key facts

- **NIH application ID:** 9834841
- **Project number:** 5R00DE026239-04
- **Recipient organization:** CINCINNATI CHILDRENS HOSP MED CTR
- **Principal Investigator:** Lindsey Anne Barske
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $247,165
- **Award type:** 5
- **Project period:** 2019-01-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9834841

## Citation

> US National Institutes of Health, RePORTER application 9834841, Prolonger progenitor maintenance sculpts the upper face (5R00DE026239-04). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9834841. Licensed CC0.

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