# A Predictive Developmental Morphospace Model of Cleft Lip

> **NIH NIH R56** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2020 · $382,339

## Abstract

SUMMARY/ABSTRACT
Normal facial morphogenesis involves the precise spatiotemporal choreography of independent facial
prominences that together must grow, contact, and fuse to form a functional upper jaw. The complexity of this
process yields multiple ways in which it may go awry, so it is unsurprising that cleft lip (CL) has both a diverse
etiology, and is also one of the most common human birth defects (~1:500-2500 births). Of the potential
causes of CL, those that impact facial prominence growth are thought to play an outsized role since later
events like contact and fusion are critically dependent on its success. That said, modeling growth has proven
to be difficult because of the complex nature of tissue movements in space and time. In this grant we take a
novel approach to the challenge of modeling facial prominence growth by combining innovative imaging
protocols with three-dimensional geometric morphometric analyses of shape. With these tools we build novel
“developmental morphospace” model of 3D embryonic craniofacial morphogenesis in the mouse and chick and
use it to generate in silico predictions of how growth variation impacts the phenotypic landscape of contact and
fusion events, both normal and abnormal. We next experimentally modulate facial prominence and brain
growth to directly test these model predictions in vivo. Support of DM predictions would validate a priori
predictions of the effect of heterogeneous genetic mutational or environmental effects on CL-liability. Moreover,
the DM would provide a generalized model for predicting how perturbations to facial prominence shape
variability, growth trajectory, and brain size can combine to impact a range of contact and fusion events.

## Key facts

- **NIH application ID:** 10241700
- **Project number:** 1R56DE029124-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Benedikt Hallgrimsson
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $382,339
- **Award type:** 1
- **Project period:** 2020-09-03 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10241700

## Citation

> US National Institutes of Health, RePORTER application 10241700, A Predictive Developmental Morphospace Model of Cleft Lip (1R56DE029124-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10241700. Licensed CC0.

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