Abstract Title
Manipulation of HIC1 and HIC2 Transcription Factors Alters apc Gene Expression in the WNT Signaling Pathway
Abstract
Hypermethylated in Cancer 1 and Hypermethylated in Cancer 2 (HIC1 and HIC2) are transcription factors that regulate the expression of several developmental genes. Loss of HIC1 or HIC2 in humans has been associated with the developmental syndromes Miller-Dieker and DiGeorge syndrome respectively. Though separate syndromes, patients with either genetic deletion exhibit craniofacial abnormalities, suggesting that HIC1 and HIC2 may both be required for craniofacial development. Using the Xenopus laevis African Clawed frog model, we have previously found that loss of HIC1 or HIC2 leads to craniofacial defects at least in part by disrupting WNT signaling. However, it is currently unknown which genes involved in the WNT signaling pathway may be regulated by HIC1/2. Here, we use the reverse transcription-polymerase chain reaction (RT-PCR) to investigate the relationship between HIC1/2 and apc, a known negative regulator of WNT signaling. We found a trend that apc expression was decreased in HIC1/2 knockdown embryos. Further studies will use in-situ hybridization to view how the expression pattern of apc in whole embryos changes when HIC1 or HIC2 expression is knocked down. Through this work, the molecular mechanisms underlying the craniofacial defects exhibited by patients with these developmental disorders may be better understood.
Manipulation of HIC1 and HIC2 Transcription Factors Alters apc Gene Expression in the WNT Signaling Pathway
Hypermethylated in Cancer 1 and Hypermethylated in Cancer 2 (HIC1 and HIC2) are transcription factors that regulate the expression of several developmental genes. Loss of HIC1 or HIC2 in humans has been associated with the developmental syndromes Miller-Dieker and DiGeorge syndrome respectively. Though separate syndromes, patients with either genetic deletion exhibit craniofacial abnormalities, suggesting that HIC1 and HIC2 may both be required for craniofacial development. Using the Xenopus laevis African Clawed frog model, we have previously found that loss of HIC1 or HIC2 leads to craniofacial defects at least in part by disrupting WNT signaling. However, it is currently unknown which genes involved in the WNT signaling pathway may be regulated by HIC1/2. Here, we use the reverse transcription-polymerase chain reaction (RT-PCR) to investigate the relationship between HIC1/2 and apc, a known negative regulator of WNT signaling. We found a trend that apc expression was decreased in HIC1/2 knockdown embryos. Further studies will use in-situ hybridization to view how the expression pattern of apc in whole embryos changes when HIC1 or HIC2 expression is knocked down. Through this work, the molecular mechanisms underlying the craniofacial defects exhibited by patients with these developmental disorders may be better understood.