HAVE GENE KNOCKOUTS CAUSED EVOLUTIONARY REVERSALS IN THE MAMMALIAN FIRST ARCH

Many recent gene knockout experiments cause anatomical changes to the jaw region of mice that several investigators claim are evolutionary r eversals. Here we evaluate these mutant phenotypes and the assertions of atavism. We argue that following the knockout of Hoxa-2, Dlx-2, MHo x, Otx2, and RAR genes, ectopic cartilages arise as secondary conseque nces of disruptions in normal processes of cell specification, migrati on, or differentiation. These disruptions cause an excess of mesenchym e to accumulate in a region through which skeletal progenitor cells us ually migrate, and at a site of condensation that is normally present in mammals but that is too small to chondrify. We find little evidence that these genes, when disrupted, cause a reversion to any primitive condition and although changes in their expression may have played a r ole in the evolution of the mammalian jaw, their function during morph ogenesis is not sufficiently understood to confirm such hypotheses. Bi oEssays 20: 245-255, 1998. (C) 1998 John Wiley & Sons, Inc.