Nested expression domains of four homeobox genes in developing rostral brain

INSIGHT into the genetic control of the identity of specific regions along the body axis of vertebrates¹ has resulted primarily from the study of vertebrate homologues of regulatory genes operating in the Drosophila trunk², but little is known about the development of most anterior regions of the body either in flies^3,4 or vertebrates. Three Drosophila genes have been identified that are important in controlling the development of the head^5-8, two of which, empty spiracles⁵ and orthodenticle⁸, have been cloned and shown to contain a homeobox^9-11. We previously cloned and characterized Emx1 and Emx2, two mouse genes related to empty spiracles that are expressed in restricted regions of the developing forebrain, including the presumptive cerebral cortex and olfactory bulbs¹². Here we report the identification of Otx1 and Otx2, which are related to orthodenticle^7,8. We have compared the expression domains of the four genes in the developing rostral brain of mouse embryos at a developmental stage, day 10 post coitum, when they are all expressed. Otx2 is expressed in every dorsal and most ventral regions of telencephalon, diencephalon and mesencephalon. The Otx1 expression domain is similar to that of Otx2, but contained within it. The Emx2 expression domain is comprised of dorsal telencephalon and small diencephalic regions, both dorsally and ventrally. Finally, Emx1 expression is exclusively confined to the dorsal telencephalon. Thus at the time when regional specification of major brain regions takes place, the expression domains of the four genes seem to be continuous regions contained within each other in the sequence Emx1 <Emx2 <Otx1 <Otx2.