Dysregulation of Grainyhead-Like 3 Expression Causes Widespread Developmental Defects
September 2021
in “
Research Square (Research Square)
”
TLDR Not having enough or having too much of the protein Grainyhead-like 3 leads to various developmental problems.
The transcription factor Grainyhead-like 3 (Grhl3) is essential for mammalian development and homeostasis. Loss of Grhl3 results in significant developmental defects such as a shortened body axis, spina bifida, syndactyly, skin barrier formation failure, and increased risk of squamous cell carcinomas due to a proliferation/differentiation imbalance in the epidermis. A novel mouse model with Grhl3 overexpression on a Grhl3-null background was created to study the effects of Grhl3 gain-of-function. While the overexpression rescued some knockout phenotypes, allowing survival into adulthood, it also caused a range of developmental issues, including hearing impairment due to structural changes in the cochlea and vestibular apparatus, hair loss, digit defects, and epidermal dysmorphogenesis. This suggests that precise regulation of Grhl3 is crucial, as both its deficiency and excess lead to widespread developmental abnormalities.
