The Transcription Factor Hypermethylated in Cancer 2 (Hic2) Influences Development of the Hatching Gland in Xenopus leavis
2024
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DiGeorge syndrome (22q11) occurs due to a hemizygous microdeletion on chromosome 22 and includes cardiac and craniofacial phenotypes among others. The hypermethylated in cancer 2 (HIC2) gene is located within the most common deletion region and previous studies showed that Hic2 is involved in cardiac development in mice. However, it is unknown if HIC2 is involved in craniofacial development. Using Xenopus leavis (African Clawed frog) embryos, we found that altered hic2 expression disrupts craniofacial cartilage formation and Xenopus hatching enzyme (xhe) gene expression was altered. We hypothesize that the development of the hatching gland is influenced by Hic2. To investigate the impact of Hic2 on hatching gland function, embryos were injected with hic2 mRNA (overexpression) or hic2 antisense morpholino oligonucleotides (knockdown). We found that Hic2 manipulation results in a broadened range of timing of embryo hatching. In situ hybridization is used to assess changes in hatching gland gene expression over developmental time. Overall, we find that altering Hic2 levels leads to changes in hatching gland gene expression and function highlighting a previously unknown developmental role for Hic2. Through continued studies, we hope to increase our understanding of how HIC2 is involved in craniofacial development and associated phenotypes in 22q11 patients.
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