Ctip2-mediated <I>Sp6</I> transcriptional regulation in dental epithelium-derived cells

Abstract

Tooth development relies on the interaction between the oral ectoderm and underlying mesenchyme, and is regulated by a complex genetic cascade. This transcriptional cascade is regulated by the spatiotemporal activation and deactivation of transcription factors. The specificity proteins 6 (Sp6) and chicken ovalbumin upstream promoter transcription factor-interacting protein 2 (Ctip2) were identified in loss-of-function studies as key transcription factors required for tooth development. Ctip2 binds to the Sp6 promoter in vivo; however, its role in Sp6 expression remains unclear. In this study, we investigated Sp6 transcriptional regulation by Ctip2. Immunohistochemical analysis revealed that Sp6 and Ctip2 colocalize in the rat incisor during tooth development. We examined whether Ctip2 regulates Sp6 promoter activity in dental epithelial cells. Cotransfection experiments using serial Sp6 promoter-luciferase constructs and Ctip2 expression plasmids showed that Ctip2 significantly suppressed the Sp6 second promoter activity, although the Sp6 first promoter activity was unaffected. Ctip2 was able to bind to the proximal region of the Sp6 first promoter, as previously demonstrated, and also to the novel distal region of the first, and second promoter regions. Our findings indicate that Ctip2 regulates Sp6 gene expression through direct binding to the Sp6 second promoter region. J. Med. Invest. 61: 126-136, February, 2014.

Isolation and characterization of dental epithelial cells derived from amelogenesis imperfecta rat

“…We also found that BMP2 could positively support amelogenesis in vitro (Miyoshi et al , ) and that SP6 could downregulate follistatin ( Fst ), a BMP antagonist (Ruspita et al , ). We further confirmed in vitro that BMP2 and wingless‐type MMTV integration site family member (Wnt) were the positive regulators of Sp6 expression (Wahyudi et al , ), while chicken ovalbumin upstream promoter transcription factor‐interacting protein 2 (Ctip2) was a negative regulator (Adiningrat et al , ). Furthermore, we found that rho‐associated protein kinase 1 (ROCK1) was positively regulated by SP6 in dental epithelium‐derived cells (Yanuaryska et al , ).…”

Bcl11b/Ctip2 in Skin, Tooth, and Craniofacial System

“…Additionally, these mice exhibit dental and periodontal defects as well as altered amelogenesis (Aïoub et al, 2007;Babajko et al, 2015;Nakatomi et al, 2018). An important transcription factor in amelogenesis, Sp6, is also a direct transcriptional target of Bcl11b (Adiningrat et al, 2014;Smith et al, 2020). Homozygous mice (Sp6-/-) have severe defects in teeth, as well as defects in skin, hair follicles, and digit formation (Nakamura et al, 2008).…”