New Mouse Model May Shed Light on Alopecia Mechanisms
Research By: Yu Lan, PhD | Rulang Jiang, PhD
Post Date: March 13, 2024 | Publish Date: March 13, 2024
Plastic Surgery | Top Scientific Achievement
Mutations in the ALX4 gene cause a rare genetic disorder known as frontonasal dysplasia-2 (FND2), which causes multiple developmental abnormalities and total alopecia. Scientists have been interested for years in gaining a better understanding of the developmental disruptions that cause the ALX4-associated abnormalities. But studies have been limited because ALX4 is expressed in many cell types during fetal development and mouse models lacking the gene die perinatally.
Now, a team at Cincinnati Children’s, led by first author Yu Lan, PhD, Division of Plastic Surgery, and corresponding author Rulang Jiang, PhD, divisions of Plastic Surgery and Developmental Biology, has succeeded in generating an Alx4f/f conditional mouse model that enables systematic investigation of ALX4 function. Their study shows when ALX4 function was inactivated in embryonic neural crest cells, the mice recapitulated the facial and skull bone defects reported in FND2 patients but exhibited a highly restricted region of hair loss over the enlarged fontanel.
On the other hand, when ALX4 function was inactivated in the embryonic cranial mesoderm, the mice showed parietal foramina at birth due to delayed parietal bone ossification but with no hair loss. These findings shed new light on the mechanisms of skull bone formation as well as alopecia.
“These mice will provide a valuable new resource for investigating the pathogenic mechanisms underlying ALX4-related developmental disorders,” Jiang says. “With regards to hair regeneration, this study shows that ALX4 plays roles in multiple cell lineages during hair follicle development.”
Further study is required to more fully understand how ALX4 expression in different cell types regulates hair growth and regeneration.
Cincinnati Children’s co-authors included Zhaoming Wu and Han Liu. This study also was supported by the Transgenic Animal and Genome Editing Facility.
Explore the 2024 Research Annual Report
| Original title: | Lineage-specific requirements of Alx4 function in craniofacial and hair development |
| Published in: | Developmental Dynamics |
| Publish date: | March 13, 2024 |
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The Research Horizons blog features news and insights about the latest discoveries and innovations developed by the scientists of Cincinnati Children's. This blog does not provide medical advice, diagnosis, or treatment.
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