A CONSERVED HOX AXIS IN THE MOUSE AND HUMAN FEMALE REPRODUCTIVE-SYSTEM - LATE ESTABLISHMENT AND PERSISTENT ADULT EXPRESSION OF THE HOXA CLUSTER GENES

The mammalian female reproductive system arises from the uniform param esonephric duct. The molecular mechanisms that establish differential development along this axis are unknown. We determined the pattern and timing of genes of the Hoxa axis in the development of the Mullerian tract. Hoxa-9, Hoxa-10, Hoxa-11, and Hoxa-13 are all expressed along t he length of the paramesonephric duct in the embryonic mouse. After bi rth, a spatial Hox axis is established, corresponding to the postnatal differentiation of this organ system in the mouse. Hoxa-9 is expresse d in the fallopian tubes, Hoxa-10 in the uterus, Hoxa-11 in the uterus and uterine cervix, and Hoxa-13 in the upper vagina. This expression pattern follows the paradigm of spatial colinearity but is a novel exc eption to temporal colinearity that has been considered typical of Hox genes. These genes remain expressed in the adult mouse and are expres sed in the same pattern in the human. The female reproductive system u ndergoes dramatic structural and functional changes during the estrous cycle and in pregnancy, retaining a high degree of developmental plas ticity. The late establishment of a Hox axis and persistent expression of Hox genes in the adult may play an important role in preserving th is plasticity.