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The specification of distinct classes of neurones in the neural tube is governed by extracellular signals and transcriptional mediators including neurogenic bHLH- and homeobox-containing genes. Despite recent insights in the transcriptional code that controls generation of neuronal subtypes in the dorsal neural tube, the mechanisms that underlie regional identity in dorsal and lateral regions of the mammalian neural tube are not well understood. The homeobox gene Lbx1 is expressed in a subset of interneurons in the early neural tube and later in dorsal parts of the spinal cord. Here we show that Lbx1 is part of the machinery that controls formation of neurones in the dorsal horn. Targeted inactivation of Lbx1 leads to a severe reduction of neurones in the dorsal horn and to down-regulation of dorsal markers such as Lmx1a from E11.5 onwards. In contrast, Pax3, another dorsally expressed homeobox gene, was up-regulated in Lbx1 mutant mice at E18.5, suggesting the existence of a negative regulatory feedback loop. Lbx1/Pax3 double-mutant mice showed an enhanced Pax3 phenotype characterized by a completely open neural tube. We suggest that Lbx1 plays a critical role in the specification of dorsal interneurons and that Lbx1 and Pax3 might act together synergistically to promote neural tube closure.

The specification of distinct classes of neurones in the neural tube is governed by extracellular signals and transcriptional mediators including neurogenic bHLH- and homeobox-containing genes. Despite recent insights in the transcriptional code that controls generation of neuronal subtypes in the dorsal neural tube, the mechanisms that underlie regional identity in dorsal and lateral regions of the mammalian neural tube are not well understood. The homeobox gene Lbx1 is expressed in a subset of interneurons in the early neural tube and later in dorsal parts of the spinal cord. Here we show that Lbx1 is part of the machinery that controls formation of neurones in the dorsal horn. Targeted inactivation of Lbx1 leads to a severe reduction of neurones in the dorsal horn and to down-regulation of dorsal markers such as Lmx1a from E11.5 onwards. In contrast, Pax3, another dorsally expressed homeobox gene, was up-regulated in Lbx1 mutant mice at E18.5, suggesting the existence of a negative regulatory feedback loop. Lbx1/Pax3 double-mutant mice showed an enhanced Pax3 phenotype characterized by a completely open neural tube. We suggest that Lbx1 plays a critical role in the specification of dorsal interneurons and that Lbx1 and Pax3 might act together synergistically to promote neural tube closure.