Embryogenesis of chimeras, twins and anterior midline asymmetries

Human spontaneous chimerism, with one body built from cells of both twins of a dizygotic (DZ) pair, is supposed to be extremely rare, arising from the exchange of blood cells through placental anastomoses. Mosaicism is supposed to be far more common, arising from single zygotes by embryonic mutation. Because typical diagnosis of mosaicism can neither identify nor exclude chimerism, ‘mosaicism’ may often be chimerism undiscovered. Evidence shows chimerism arises primarily from DZ embryo fusion and is not rare, although it has negligible probability under the hypothesis of independent double ovulation and independent embryogenesis. If, instead, DZ twin embryos begin development as a single cell mass, chimerism is likely. This would be consistent with observations that DZ twins develop as differently from singletons as monozygotic twins do with regard to embryogenic establishment of asymmetries of midline neural-crest-driven structures of brain, face and heart. Chimerism is a significant component of human embryonic development that deserves closer attention as a mechanism of developmental variation. The ‘common knowledge’ understanding of twinning mechanisms is at best inadequate. The importance of the difference lies in what we can learn from chimerism about human embryogenesis and the cellular origins of structures and functions basic to the business of becoming human.