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Sex combs reduced (Scr), a Hox gene located in the Antennapedia complex of Drosophila melanogaster, is required for the proper development of the labial and first thoracic segments. The Tribolium castaneum genetically defined locus Cephalothorax (Cx) is a candidate Scr ortholog based on the location of Cx in the beetle Homeotic complex and mutant effects on the labial and first thoracic segments. To address this hypothesis, we have cloned and characterized the Tribolium ortholog of Scr (TcScr). The transcription unit is less complex and encodes a smaller protein than Scr. The predicted amino acid sequence of the Tribolium protein shares motifs with orthologous proteins from multiple species. In addition, we have analyzed the TcScr expression pattern during embryonic development. TcScr is expressed in parts of the maxillary, labial, and first thoracic segments in a pattern similar to but not identical to Scr. Furthermore, TcScr RNA interference results in a phenocopy of the Cephalothorax (Cx) mutant phenotype in which the labial palps are transformed into antennae and the head and first thoracic segment are fused. All of the available results indicate that Cx is the Tribolium ortholog of Scr.