Pancreatic Development Antibody Sampler Kit #85653

The pancreatic duodenal homeobox gene-1 (Pdx1) is a transcription factor that contributes to pancreas development, pancreatic β-cell differentiation, and mature β-cell function (1,2). It plays an essential role in the commitment of endoderm to a pancreatic and later β-cell phenotype (2,3). In the mature pancreas, Pdx1 expression is more restricted to the pancreatic β-cells (3), where it promotes the expression of genes important for β-cell functions (4-6). Mutations of the corresponding PDX1 gene may be associated with diabetes and cases of pancreatic insufficiency (7).

The homeodomain protein NKX6.1 is a transcription factor that regulates pancreatic β-cell development (2). Overexpressed NKX6.1 stimulates rat pancreatic β-cell proliferation and increases glucose-stimulated insulin secretion (GSIS) (8). The effect on GSIS was shown to be mediated by the upregulation of prohormone VGF expression and the subsequent potentiation by TLQP-21, a peptide derived from VGF (9). Both nuclear receptors Nr4a1 and Nr4a3 are essential for pancreatic β-cell proliferation driven by overexpressed NKX6.1 (10). In addition, studies suggest that NKX6.1 is a suppressor for epithelial-mesenchymal transition (EMT), leading to inhibition of tumor metastasis (11).

Paired box (PAX) proteins are a family of transcription factors that play important and diverse roles in animal development (12). Nine PAX proteins (PAX1-9) have been described in humans and other mammals. They are defined by the presence of an amino-terminal "paired" domain, consisting of two helix-turn-helix motifs, with DNA binding activity (13). PAX proteins are classified into four structurally distinct subgroups (I-IV) based on the absence or presence of a carboxy-terminal homeodomain and a central octapeptide region (13). PAX proteins play critically important roles in development by regulating transcriptional networks responsible for embryonic patterning and organogenesis (14); a subset of PAX proteins also maintains functional importance during postnatal development (15). Research studies have implicated genetic mutations that result in aberrant expression of PAX genes in a number of cancer subtypes (12-14), with members of subgroups II and III identified as potential mediators of tumor progression (13).

Neurogenic differentiation factor 1 (NeuroD1) is a member of the basic helix-loop-helix (bHLH) family of transcription factors. These proteins function by forming heterodimers with E-proteins and binding to the canonical E-box sequence CANNTG (16,17). NeuroD1 is crucially important in both the pancreas and the developing nervous system and plays a large role in the development of the inner ear and mammalian retina (18). Mice lacking NeuroD1 become severely diabetic and die shortly after birth due to defects in β-cell differentiation (17-20).

MAFA and MAFB belong to the musculoaponeurotic fibrosarcoma (MAF) family of basic leucine-zipper transcription factors (21). In the mouse embryo, MAFA expression is first detected at E13.5, restricted to Nkx6.1-positive insulin-producing islet cells (22). Expression of the MAFA gene is sensitive to physiological glucose levels, and genomic targets regulated by MAFA include β-cell transcription factors (e.g., PDX1) and the insulin gene (22,23). In mouse embryo, MAFB expression is first detected at E10.5 (24,25). Early in development, MAFB drives differentiation of both glucagon-producing α-cells and insulin-producing β-cells in the pancreas, but later plays a more decisive role in the maturation and maintenance of functional α-cells (26,27).