Figure 7. Phylogeny of endoderm enhancers along with transition from ventral lungs to dorsal gas bladder.

The figure summarizes phylogeny of the two enhancers, MACS1 orthologues and Block-2, integrating their enhancer activity in mouse and medaka. MACS1 orthologues are present in the cartilaginous fish and bony fish lineages. Block-2 emerged in the non-teleost ray-finned fish lineage, and is conserved in the teleost fishes including euteleost fishes. Spotted gar and teleoast fishes have both MACS1 and Block-2 in the same rnf32 intron. Exceptionally, both enhancers are absent in zebrafish. Notably, the transgenic reporter assay indicated that MACS1 induced reporter expression ventrally in the laryngeal epithelium and/or the laryngotracheal groove in mouse embryos, but not in medaka larvae, whereas Block-2 induced expression in dorsal epithelia of the pharynx and oesophagus in both mouse embryos and medaka larvae. This dorsoventral axis polarity is relevant to the position where the lungs and gas bladder evaginate from the posterior pharynx. Asterisks mark species analysed only by Southern blotting. Highly diverged MACS1 orthologues are noted in parentheses. Physostomous fishes retain pneumatic duct until adulthood, and many of them have lost respiratory function in the gas bladder⁴¹. Euteleost fishes including medaka, stickleback, Nile tilapia have physoclistous gas bladder, which is completely separated from the foregut in adulthood⁷⁰. ni, no information; nt, not tested.