Differential transcription of Barhl1 homeobox gene in restricted functional domains of the central nervous system suggests a role in brain patterning.
The mouse Barhl1 homeogene, member of the BarH subfamily, play a crucial role in the cerebellum development and its human ortholog BARHL1 has been proposed as a positional and functional candidate gene for the Joubert syndrome, a form of cerebellar ataxia. The Barhl1 expression has been demonstrated to be induced by the transcription factor Math1 involved in BMP responses. We isolated the mouse Barhl1 by screening of a cDNA library with the Xenopus Xvent-2, member of the BarH subfamily, which acts in the BMP4 pathway during embryonic patterning and neural plate differentiation. We studied the detailed Barhl1 expression pattern and showed its transcription in spatio-temporally and functionally restricted domains of the developing central nervous system (CNS). Using our new optical microscopy technology, we compare the transcript steady state level and cell density in the Barhl1-expressing regions. We found that Barhl1 was transcribed in superior and inferior colliculi in the dorsal mesencephalon at a relatively low transcriptional level. In the diencephalon, Barhl1 was found higher expressed first within the basal plate and later in the mammillary region. In the cerebellum, Barhl1 showed the highest transcriptional level restricted to the anterior and posterior rhombic lips giving rise to the external and internal cerebellar granular cells and to the deep nuclei. In the spinal cord, Barhl1 showed similar expression level than in the cerebellum and is delimited to a subset of dorsal interneurons. Therefore, our results indicated that Barhl1 homeodomain gene is exclusively transcribed in restricted CNS domain at differential transcription levels which suggest a highly regulated transcriptional mechanism. In addition, these regional and cellular specificities indicated that Barhl1 may be involved in the differentiation of the specific subsets of neuronal progenitors.
Rachidi
Mohammed
M
Institut d'Embryologie Cellulaire et Moléculaire, CNRS UMR 7128, Collège de France, 94736 Nogent-sur-Marne, France. mrachidi2@yahoo.fr
Lopes
Carmela
C
D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000033:anatomy & histology / Q000254:growth & development* / Q000473:pathology*; D004622:Embryo, Mammalian / Q000033:anatomy & histology / Q000502:physiology; D015870:Gene Expression; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D017403:In Situ Hybridization; D051379:Mice; D008969:Molecular Sequence Data; D009024:Morphogenesis; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D014158:Transcription, Genetic
C485866:Barhl1 protein, mouse; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D012097:Repressor Proteins