PANCREATIC BETA-CELLS EXPRESS A DIVERSE SET OF HOMEOBOX GENES

Homeobox genes, which are found in all eukaryotic organisms, encode tr anscriptional regulators involved in cell-type differentiation and dev elopment. Several homeobox genes encoding homeodomain proteins that bi nd and activate the insulin gene promoter have been described. In an a ttempt to identify additional beta-cell homeodomain proteins, we desig ned primers based on the sequences of beta-cell homeobox genes cdx3 an d lmx1 and the Drosophila homeodomain protein Antennapedia and used th ese primers to amplify inserts by PCR from an insulinoma cDNA library. The resulting amplification products include sequences encoding 10 di stinct homeodomain proteins; 3 of these proteins have not been describ ed previously. In addition, an insert was obtained encoding a splice v ariant of engrailed-2, a homeodomain protein previously identified in the central nervous system. Northern analysis revealed a distinct patt ern of expression for each homeobox gene. Interestingly, the PCR-deriv ed clones do not represent a complete sampling of the beta cell librar y because no inserts encoding cdx3 or lmx1 protein were obtained. Beta cells probably express additional homeobox genes. The abundance and d iversity of homeodomain proteins found in beta cells illustrate the re markable complexity and redundancy of the machinery controlling beta c ell development and differentiation.