Early steps in the evolution of multicellularity: deep structural and functional homologies among homeobox genes in sponges and higher metazoans.

The sponge homeobox gene EmH-3 had not been attributed to any homeobox family. Comparative promoter and homeodomain sequence analyses suggest that it is related to the Hox11 gene, which belongs to the Tlx homeobox family. Hox11 is highly expressed in proliferating progenitor cells, but expression is downregulated during cell differentiation. Using reporter gene methodology, we monitored function of the sponge EmH-3 promoter transfected into human erythroleukemia K562 cells. These cells express the Tlx/Hox11 gene constitutively, and downregulate its expression upon differentiation. The same pattern of expression and downregulation was observed for the sponge reporter construct. We propose that Tlx/Hox11 genes have structural and functional homologies conserved in phylogenetically distant groups, that represent a deep homology in the regulation of cell proliferation, commitment and differentiation.