1) Inst. Biolog. Sci., Univ. Tsukuba, Tsukuba 305, Japan. 2) Zoologishes Institut der Univ. Basel, CH-4051 Basel, Switzerland. 3) Internat. Inst. Genet. & Biophys. CNR, I-80125 Napoli, Italy.
The question of how the development of brain is genetically controlled is one of the central issues of neural science. Neuroanatomical studies in vertebrates indicate that the developing brain may be organized into distinct neuromeric regions that reflect a basic metameric organization. Similarly, morphological and developmental studies on the insect brain also suggest an underlying metameric organization.
We have shown that the Drosophila brain is composed of three segmental neuromeres, b1, b2 and b3, which may correspond to proto-, deuto, and tritocerebrums in classic neuroanatomy. Two of the evolutionarily conserved homeobox genes, orthodenticle (otd) and empty spiracles (ems) are segmentally expressed in the developing Drosophila brain. The otd gene is expressed predominantly in the anterior neuromere b1 whereas the ems gene expression is restricted to the two posterior neuromeres b2 and b3. Mutation of otd eliminates the first brain neuromere; mutation of ems eliminates the second and third neuromeres. Moreover, we find that otd gene activity is also required for the development of the dorsal protocerebrum of the adult brain.
Since the mammalian homologs of the otd/Otx and ems/Emx genes are expressed in, and required for the development of the fore- and the midbrain in higher vertebrates, fundamental genetic programs of the development of the cephalic structures including the brain might be conserved. As a way to examine the possible conservation of the cephalic developmental programs, we have introduced the human Otx homologs into flies, and examined their developmental control potentials in a fly otd mutant, ocelliless, which fail to develop ocelli and associated vertex structures as well as the protocerebral bridge in the brain. By inducing expression of the transgene via a heat shock promoter, we find that both the human Otx1 and Otx2 genes are as potent as the fly otd gene in rescue of the epidermal defects in the mutant. We discuss our results in the light of the origin of cephalogenesis and brain formation in evolution (supported by the Swiss NSF and the Univ. Tsukuba).