EXPRESSION AND REGULATION OF LHX6 AND LHX7, A NOVEL SUBFAMILY OF LIM HOMEODOMAIN ENCODING GENES, SUGGESTS A ROLE IN MAMMALIAN HEAD DEVELOPMENT

LIM-homeobox containing (Lhx) genes encode trascriptional regulators w hich play critical roles in a variety of developmental processes. We h ave identified two genes belonging to a novel subfamily of mammalian L hx genes, designated Lhx6 and Lhx7. Whole-mount in situ hybridisation showed that Lhx6 and Lhx7 were expressed during mouse embryogenesis in overlapping domains of the first branchial arch and the basal forebra in, More specifically, expression of Lhx6 and Lhx7 was detected prior to initiation of tooth formation in the presumptive oral and odontogen ic mesenchyme of the maxillary and mandibular processes. During tooth formation, expression was restricted to the mesenchyme of individual t eeth. Using explant cultures, me have shown that expression of Lhx6 an d Lhx7 in mandibular mesenchyme was under the control of signals deriv ed from the overlying epithelium; such signals were absent from the ep ithelium of the non-odontogenic second branchial arch. Furthermore, ex pression studies and bead implantation experiments in vitro have provi ded strong evidence that Fgf8 is primarily responsible for the restric ted expression of Lhx6 and Lhx7 in the oral aspect of the maxillary an d mandibular processes. In the telencephalon, expression of both genes was predominantly localised in the developing medial ganglionic emine nces, flanking a Fgf8-positive midline region. We suggest that Fgf8 an d Lhx6 and Lhx7 are key components of signalling cascades which determ ine morphogenesis and differentiation in the first branchial arch and the basal forebrain.