# Genetic, hormonal, and mechanical influences on sexually dimorphic bone development

> **NIH NIH P20** · CLEMSON UNIVERSITY · 2021 · $308,797

## Abstract

Sex dimorphism, phenotypic differences between males and females, is widespread in the musculoskeletal 
system. Within the craniofacial skeleton, this variation can result in differential biting mechanics and common 
conditions that can require surgical correction. For instance, temporomandibular joint dysfunction affects 35 
million patients in the US, with 3 to 8 times more women than men affected. The central hypothesis of this 
grant is that craniofacial variation between sexes results from interactions of sex-determining genes and 
developmental genes (Aim 1), the hormone environment (Aim 2), and mechanical forces (Aim 3). To assess 
this, we will capitalize on the unparalleled natural craniofacial variation among the evolutionary radiation of 
non-model cichlid fishes. Given that cichlid facial variation mimics human facial variation and the molecular 
control of facial development is conserved across vertebrates, this may yield novel insights into the regulation 
of sexual dimorphism in human faces. In Aim 1, we will investigate the origins of sex-specific bone shape, 
density, and material properties using three cichlid species that show diverse adult morphologies. Notably, 
all three species demonstrate sexual dimorphism, but the patterns of dimorphism are species-specific. We 
will use micro-CT scanning, histological analysis, and RNA-seq to assess the cellular and transcriptional 
drivers of variation in sexual dimorphism during development. In Aim 2, we will alter the sex hormone 
environment and assess the resultant effects on morphology, the activity of chondrogenic and osteogenic 
processes, and gene expression. This will clarify the role of hormones in early bone patterning, as well as 
potential mechanisms through which ubiquitous endocrine disrupting chemicals in the environment may 
produce variation in facial development. Applying these hormones in closely-related cichlids (comparable to 
comparing different mouse strains), enables additional investigation of gene by environment (GxE) 
interactions. In Aim 3, we will capitalize on the fact that cichlids forced to eat with alternate feeding strategies 
(biting versus suction feeding) have a plastic response and remodel their facial skeleton. We will assess how 
remodeling is distinct between the sexes in terms of shapes produced and cellular activity, with potential 
implications for differential exercise-induced remodeling between males and females. In all, we will assess 
interactions of sex with developmental genes, hormones, and mechanical strain. This work will provide 
insights on the cellular and molecular mechanisms that generate variation in bone shape and may influence 
prevalence or severity of musculoskeletal medical issues between sexes.

## Key facts

- **NIH application ID:** 10479428
- **Project number:** 5P20GM121342-04
- **Recipient organization:** CLEMSON UNIVERSITY
- **Principal Investigator:** Kara E Powder
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $308,797
- **Award type:** 5
- **Project period:** 2021-08-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10479428

## Citation

> US National Institutes of Health, RePORTER application 10479428, Genetic, hormonal, and mechanical influences on sexually dimorphic bone development (5P20GM121342-04). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10479428. Licensed CC0.

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