The Mouse homeobox gene BarhII plays a central role in cerebellum development and its expression is activated by the transcription factor MathI which is involved in bone morphogenetic protein response pathways. We studied the human ortholog BARHLI and we found that human, mouse, monkey, rat, and zebrafish orthologs were highly conserved and are members of the Bat-H homeogene family, containing Drosophila BarH1 and BatH2. The N-terminus of BARHLI protein presents two FIL domains and an acidic domain rich in serine/threonine and proline, while the C-terminus contains a canonical proline-rich domain. Secondary structure analysis showed that outside the three helixes of the homeodomain, BARHLI protein has essentially random coil structure. We isolated BARHLI and defined its expression pattern in human embryonic and fetal central nervous system (CNS) and compared it to the mouse BarhII transcription. BARHLI mRNA was found exclusively in the CNS restricted to p1-p4 prosomeres of the diencephalon, to the dorsal cells of the mesencephalon, to the dorsal d11 sensory neurons of the spinal cord, and to the rhombic lips yielding the cerebellar anlage. Detailed analysis of BARHLI expression in fetal cerebellar cell layers using our new optic microscopy technology showed BARHLI expression in external and internal granular cells and also in mouse adult granular cells, in agreement to BarhII null mouse phenotype affecting the differentiation and migration of granular cells. These findings indicate that the regional and cellular specificities of BARHLI transcriptional control well correspond to the mouse BarhII transcription and suggest a potential role of this gene in the differentiation of BARHLI-expressing nueronal progenitors involved in the pattern formation of human cerebral and cerebellar structures. (c) 2005 Elsevier Inc. All rights reserved.