Dynamic expression of Tbx2 and Tbx3 in developing mouse pancreas

Abstract

Tbx2 and Tbx3 are closely related members of the T-box family of transcription factors that are important regulators during normal development as well as major contributors to human developmental syndromes when mutated. Although there is evidence for the involvement of Tbx2 and Tbx3 in pancreatic cancer, so far there are no reports characterizing the normal expression pattern of these genes in the pancreas. In this study, we examined spatial and temporal expression of Tbx2 and Tbx3 in mouse pancreas during development and in the adult using in situ hybridization and immunohistochemistry. Our results show that Tbx2 and Tbx3 are both expressed in the pancreatic mesenchyme throughout development beginning at embryonic day (E) 9.5. In addition, Tbx2 is expressed in pancreatic vasculature during development and in epithelial-derived endocrine and ductal cells during late fetal stages, postnatal development and in adult pancreas. In contrast, Tbx3 is expressed in exocrine tissue in the postnatal and adult pancreas. Further our results demonstrate that Tbx2 and Tbx3 are expressed in tumor-derived endocrine and exocrine cell lines, respectively. These dynamic changes in the expression pattern of these transcription factors lay the foundation for investigation of potential roles in pancreas development.

Insm1 promotes endocrine cell differentiation by modulating the expression of a network of genes that includes Neurog3 and Ripply3

“…As mentioned above, members of this class of proteins have been shown to bind and suppress the activity of T-box transcription factors. Previous reports ( Begum and Papaioannou, 2011 ; Oropez and Horb, 2012 ) have shown that Tbx2 is expressed in pre-endocrine cells, and our current findings indicate that it is upregulated in the absence of Insm1 . Thus, given that Tbx2 was previously shown to promote cell proliferation ( Vance et al, 2005 ), Ripply3 might function by antagonizing Tbx2 activity in differentiating endocrine cells.…”

Overexpression of Tbx3 Predicts Poor Prognosis of Patients with Resectable Pancreatic Carcinoma

“…Tbx3 is expressed in exocrine tissue in the postnatal, adult pancreas and tumor-derived exocrine cell lines (Washkowitz et al, 2012). Moreover, it is closely related to pancreatic lesions, such as solid pseudopapillary neoplasm (SPN), well-differentiated pancreatic neuroendocrine neoplasms (PENE) and PC (Hansel et al, 2004;Cavard et al, 2009;Begum and Papaioannou, 2011). In the present study, we examined the Tbx3 expression at both mRNA and protein levels in PC samples, and analyzed the correlations between Tbx3 expressions and various clinicopathological parameters.…”

The T-box gene family: emerging roles in development, stem cells and cancer

“…• Increased levels of TBX2 and TBX3 are associated with several types of cancer, including melanoma, pancreatic and mammary carcinoma, and the genes are expressed during normal development of the corresponding tissues (Abrahams et al, 2010;Begum and Papaioannou, 2011;Carreira et al, 1998;Douglas and Papaioannou, 2013;Rowley et al, 2004). Both genes repress the cyclin-dependent kinase inhibitors p16…”