# Origins of Sexual Dimorphism in the Craniofacial Skeleton

> **NIH NIH P20** · CLEMSON UNIVERSITY · 2024 · $229,434

## Abstract

SUMMARY
Phenotypic differences between males and females, termed sexual dimorphism, are a critical biological variable.
Sex-based variation produces distinct biting kinematics, differential prevalence and severity of musculoskeletal
conditions, and a variety of medical issues often requiring surgery. Despite these data indicating a clear impact
of sex on craniofacial function and health, a critical gap in our knowledge includes the developmental stage at
which males and females begin to differ in phenotype, including in common model organisms such as mice,
chickens, and fishes. Further, we do not know the underlying mechanisms that generate variation in sexual
dimorphism, such as the effects of genetic background and hormone signaling, particularly in early facial
development. We model human sexual dimorphism using cichlid fishes, which have evolved exceptional
craniofacial variation, enable easy manipulation of embryonic development through immersion of animals in
chemicals, and mirror human sexual dimorphism in terms of effects on the mandible and variation due to genetic
background. Given that the molecules that control facial development are highly conserved across vertebrates,
this work may identify new mechanisms and genes that regulate musculoskeletal variation in humans. For
example, Pdgfra regulates orofacial clefting in humans, mice, and fishes. The central question of this project is
how sex generates functional variation in shape of the craniofacial skeleton. This Phase 2 application will focus
on morphology, developmental time, and candidate genes to lay the foundations for future R01 applications
focused on cellular and molecular mechanisms. In Aim 1, we will assess developmental origins of sexual
dimorphism in bone shape and material properties between the sexes. We will also evaluate genetic risk factors
that add further variation to sex-based phenotypes. These data will define when sex generates variation in the
craniofacial skeleton and identify specific bones, timepoints, and candidate genes for a future R01 grant. In Aim
2, we will assess the morphological role of sex hormones in embryonic bone development. We predict that these
hormones not only regulate bone patterning in both sexes, but variation in hormone signaling drives male-female
differences and species-specific presentation of sexual dimorphism. Completion of this aim will extend our
knowledge of hormones in adult bone biology to embryonic stages, which is currently a major gap in our
understanding. We will also identify developmental windows and critical cell types for future mechanistic study
in an R01 application. This project was conceptualized for an initial SC-TRIMH due to potential integration within
this group and utilizes the Pre-clinical Assessment Core (PAC), Multiscale Computational Modeling (MCM) core,
Advanced Fabrication & Testing (AFT) core, and the Administrative Core. It also synergizes with two other
COBRES at Clemson University that support the Cl...

## Key facts

- **NIH application ID:** 10912643
- **Project number:** 5P20GM121342-07
- **Recipient organization:** CLEMSON UNIVERSITY
- **Principal Investigator:** Kara E Powder
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $229,434
- **Award type:** 5
- **Project period:** 2018-09-15 → 2028-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10912643

## Citation

> US National Institutes of Health, RePORTER application 10912643, Origins of Sexual Dimorphism in the Craniofacial Skeleton (5P20GM121342-07). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10912643. Licensed CC0.

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