GALIS, F.; METZ, J.A.J.; Leiden University; idem: Developmental Mechanisms underlying the Conservation of the seven cervical Vertebrae

The number of cervical vertebrae is extremely conserved in mammals. Yet, studies on fetal deaths in humans show that new mutants with an effect on this number are common. This indicates that evolutionary conservation is caused by strong stabilizing selection. The cause for the selection appears to be that mutations with an effect on the number of cervical vertebrae almost invariably lead to deleterious pleiotropic effects in other parts of the body. Changes in the number of cervical vertebrae usually involve homeotic shifts of several cervical and thoracic vertebrae. These shifts are due to changes in the early antero-posterior (A-P) patterning of the paraxial mesoderm. We have investigated the literature for links between the A-P patterning of the paraxial mesoderm and other patterning and morphogenetic processes. Many processes were found to be linked to the A-P patterning of the paraxial mesoderm including left-right patterning, limb induction and neural tube closure. On the basis of these links we predict a coupling between specific anomalies due to disturbances of these processes and changes in the number of cervical vertebrae. We will discuss support for these predictions from data on fetal deaths. We conclude that the links that we have found to exist between the A-P patterning of the paraxial mesoderm and other processes are indeed underlying the pleiotropic effects that are associated with changes in the number of cervical vertebrae. Furthermore, we conclude that the A-P patterning of the paraxial mesoderm plays a central role during the neurula stage and that the conservation of this early, most conserved, part of the phylotypic stage in mammals appears to go hand-in-hand with the conservation of the number of cervical vertebrae.