Homeogenes in mammalian development and the evolution of the cranium and central nervous system

Homeobox-containing genes, the homeogenes, are transcriptional regulators conserved in numerous animal groups. In the fruit fly they specify the identity of certain spatial units of development. We present a somewhat subjective summary of the advance triggered in vertebrate developmental biology by the discovery of the homeobox. Emphasis is placed on one group, the Antp (Antennapedia)-like homeogenes. Antp-like homoeogenes are expressed in overlapping longitudinal areas of the neuroectoderm and mesoderm. The genomic organization of these genes is most uniquely connected with their expression. They are organized into unlinked clusters of 8-10 loci. The linear order of genes within the clusters is highly conserved both among clusters within a species and among clusters of distant species. Expression of these genes along the longitudinal body axis uniformly follows a 5'-posterior-3'-anterior rule. Their anterior border of expression stops abruptly at the hindbrain. A hypothesis is proposed, which suggests that much of the mid- and hindbrain, as well as the craniofacial structures, are newly acquired in the evolution of vertebrates, and do not utilize the more ancient Antp-like homeogenes. We assume that these organs have a different group or groups of spatially specific transcriptional regulators.