The Biology Lair

The debate on whether platyhelminths (or flatworms) were originally simply organized animals or secondarily simplified from a more complex ancestor is in fact a very old one and has always been linked with the controversy about the origin of bilaterally symmetrical metazoans (Bilateria). However, in the past decades, the vehement point of view of Hyman (that is genuine simplicity) has been dominating. The flatworms, in most textbooks of zoology, are uncritically presented as the first group emerging in the history of the bilaterians. In some books with insights into embryogenesis, the flatworms are placed emerging at the base of the protostomes (Brusca and Brusca, 1990; Nielsen, 1995). But the basic assumption remains that evolution proceeded from a simple acoelomate condition to the more complex coelomate organisation and that flatworms are modern representatives of the former step. Before challenging this dogma on molecular grounds, it is useful to expose two important historical concepts which have been in competition for explaining the origin of the bilaterians: the planuloid-acoeloid theory and the archecoelomate theory (reviewed in Willmer, 1990). We can then ask what predictions can be made for the topology of the metazoan tree under each of these schemes.

The sphingosine 1-phosphate receptor 1 (S1P₁) and its ligand, sphingosine 1-phosphate (S1P), have now emerged as critical regulators of lymphocyte trafficking, vascular development and integrity, and immunity. S1P₁ is targeted by the phosphorylation product of fingolimod, which has been approved for the treatment of multiple sclerosis. The recent progress in the structural biology of heterotrimeric guanine nucleotide–binding protein (G protein)–coupled receptors has now enabled the elucidation of the structure of S1P₁. Analysis of the structure, along with structure activity and mutagenesis analysis, highlighted key interactions associated with the binding of S1P and agonists and suggested that the ligand may gain access to the binding pocket by lateral diffusion within the plasma membrane. The S1P₁ crystal structure will be helpful for designing ligands that specifically target S1P₁.