Barhl1, a gene belonging to a new subfamily of mammalian homeobox genes, is expressed in migrating neurons of the CNS

The BarH1 and BarH2 (Bar) Drosophila genes are homeobox-containing genes, w hich are required for the fate determination of external sensory organs in the fly. By means of a bioinformatic approach, we have identified in mouse and human two homeobox genes highly related to the Bar Drosophila genes, Ba rhl1 and Barhl2, While Barhl1 represents a novel gene, Barhl2 turned out to correspond to the mBH1 cDNA recently described in rat. We isolated and seq uenced the full-length mouse Barhl1 and mapped both the human BARHL1 and BA RHL2 genes to chromosomes 9q34 and 1p22, respectively, Detailed analysis of the murine Barhl1 expression pattern by in situ hybridization revealed tha t this transcript is exclusively expressed in restricted domains of the dev eloping CNS, which suggests that this gene, similar to its Drosophila count erparts BarH1 and BarH2: may play a crucial role in cell fate determination of neural structures. In particular, Barhl1 showed specific domains of exp ression in the diencephalon and in the rhombencephalon where it was found t o be expressed in migrating cells giving rise to the cerebellar external gr anular layer and to specific populations of dorsal sensory interneurons of the spinal cord. Thus, Barhl1 function may be required for the generation o f these specific subtypes of neuronal progenitors. Furthermore, the mapping assignment and the expression pattern make BARHL1 an attractive positional candidate gene for a form of Joubert syndrome, a rare developmental anomal y of the cerebellum in humans.