Region-specific gastrointestinal Hox code during murine embryonal gut development

Hox genes encode transcription factors, and they are involved in the specification of each body part along the anteroposterior (AP) body axis during embryogenesis. To clarify AP pattern formation of the digestive tract, the expression patterns of Hox genes belonging to paralogous groups 4 and 5, and parts of groups 6 and 7, were systematically examined by whole-mount and section in situ hybridization. The Hox gene expression pattern of paralogous groups 4-9 in the developing gut at 12.5 days post-coitum was fully examined. All HoxA and HoxB genes in paralogous groups 4-8 were expressed in the stomach, in contrast to the HoxC and HoxD genes. In the midgut region, all Hox cluster genes showed colinear expression within each cluster, yielding the Hox code; the more 3' located genes were expressed more rostrally and the 5' group genes more caudally. The colinear expression of HoxA and HoxB cluster genes started from the duodenum, that of HoxC cluster genes started from the jejunum, and HoxD cluster genes were expressed in the caudal part of the midgut, ileum and cecum. In the hindgut region, HoxD cluster genes and Abd-B family genes were expressed. Thus, a different Hox code seems to exist in each subdomain of developing gut (foregut, midgut and hindgut). The visceral mesoderm restricted expression also suggested that the Hox code primarily functions in mesenchymal specification, and then leads to the regional differentiation of gut subdomains as the result of epithelial-mesenchymal interactions.