BARHL1 homeogene, the human ortholog of the mouse Barhl1 involved in cerebellum development, shows regional and cellular specificities in restricted domains of developing human central nervous system.
The mouse homeobox gene Barhl1 plays a central role in cerebellum development and its expression is activated by the transcription factor Math1 which is involved in bone morphogenetic protein response pathways. We studied the human ortholog BARHL1 and we found that human, mouse, monkey, rat, and zebrafish orthologs were highly conserved and are members of the BarH homeogene family, containing Drosophila BarH1 and BarH2. The N-terminus of BARHL1 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, BARHL1 protein has essentially random coil structure. We isolated BARHL1 and defined its expression pattern in human embryonic and fetal central nervous system (CNS) and compared it to the mouse Barhl1 transcription. BARHL1 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 dl1 sensory neurons of the spinal cord, and to the rhombic lips yielding the cerebellar anlage. Detailed analysis of BARHL1 expression in fetal cerebellar cell layers using our new optic microscopy technology showed BARHL1 expression in external and internal granular cells and also in mouse adult granular cells, in agreement to Barhl1 null mouse phenotype affecting the differentiation and migration of granular cells. These findings indicate that the regional and cellular specificities of BARHL1 transcriptional control well correspond to the mouse Barhl1 transcription and suggest a potential role of this gene in the differentiation of BARHL1-expressing neuronal progenitors involved in the pattern formation of human cerebral and cerebellar structures.
Lopes
Carmela
C
EA 3508 Université Paris 7-Denis Diderot, Paris, France.
Delezoide
Anne-Lise
AL
Delabar
Jean-Maurice
JM
Rachidi
Mohammed
M
D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D002531:Cerebellum / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D012097:Repressor Proteins; D017386:Sequence Homology, Amino Acid
C412478:BARHL1 protein, human; C485866:Barhl1 protein, mouse; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D012097:Repressor Proteins