# Determining the Role of Extracellular Matrix Compliance and Composition on Facial Morphogenesis

> **NIH NIH F32** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2022 · $70,602

## Abstract

PROJECT SUMMARY
Facial morphogenesis involves directed outgrowth of the facial primordia until they appose and fuse with one
another. Currently, outgrowth of primordia is considered to be driven primarily by bulk tissue displacement
caused by proliferation gradients in the mesenchymal tissue. However, our lab and others have found that other
mechanisms, such as directed cellular migration and epithelium guided growth, likely contribute as well. In the
limb bud, tensile forces generated by the ectoderm have been shown to direct cellular orientation and growth,
and proliferation gradients across the limb bud cannot accurately model morphogenesis without incorporating
directed cellular behaviors. Our lab has previously shown that mesenchymal cells in the face are polarized and
that activation of fibroblastic growth factor (FGF) signaling disrupts this polarity while causing aberrant outgrowth
of the primordium. The extracellular matrix (ECM) around cells provides the structural scaffolding required to
generate and guide force through tissue, and the ECM in the epithelium may guide or constrain growth regionally.
I hypothesize that the ECM directs morphogenesis in the face via regional differences in composition and
compliance. I will test this hypothesis with two main aims. In the first aim I will examine how FGF signaling affects
ECM physical properties and cellular organization in the facial primordium. I will quantitatively map the
composition of ECM proteins and ECM compliance across the face with confocal microscopy and atomic force
microscopy, then relate regional differences in these measures to facial shape change. This aim will elucidate
mechanisms by which molecular signaling of fibroblastic growth factor controls morphogenesis through the ECM
and cellular organization. In the second aim, I will increase or decrease tissue compliance directly by altering
collagen crosslinking, then repeat the same analyses as the first aim. The second aim will determine if ECM
stiffness directs outgrowth directly while the mesenchyme passively conforms around it, or if there is feedback
between ECM and cells that actively remodel the environment to direct growth. Failure of the facial primordium
to appose and fuse leads to facial clefting. Understanding the role of ECM in directional growth is important for
understanding the etiology of birth defects in the face.

## Key facts

- **NIH application ID:** 10306333
- **Project number:** 5F32DE030359-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Nicholas Jean Hanne
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $70,602
- **Award type:** 5
- **Project period:** 2020-12-01 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10306333

## Citation

> US National Institutes of Health, RePORTER application 10306333, Determining the Role of Extracellular Matrix Compliance and Composition on Facial Morphogenesis (5F32DE030359-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10306333. Licensed CC0.

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