DEVELOPMENTAL FUNCTIONS OF MAMMALIAN HOX GENES

The structure of the four murine Hox complexes and the co-ordinate exp ression patterns of Hox genes have been elucidated for almost a decade . However, clues about their developmental functions have been recentl y uncovered from the analysis of loss-of-function mutants generated by the gene targeting technique, as well as from transgenic mice with al tered Hox gene expression domains. The 'anterior' Hox genes control th e morphogenetic programme of specific hindbrain segments (rhombomeres) or pharyngeal arch neural crest derivatives, Various studies indicate that Hox gene products act in a region-specific, combinatorial and pa rtly redundant manner to specify the identities of developing vertebra e, In addition, 'posterior' HoxA and HoxD genes act coordinately to co ntrol the growth and morphogenesis of skeletal structures along the pr oximodistal axis of developing limbs. Studies in other vertebrate mode l systems suggest that the evolution of Hox gene functions has allowed for the acquisition of specific morphological features along both the vertebral column and limbs of tetrapods. Gene targeting studies have also revealed region-specific functions of Hox genes along the develop ing digestive and genito-urinary tracts.