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Pax-2 regulatory sequences that direct transgene expression in the developing neural plate and external granule cell layer of the cerebellum
Expression of Pax-2 in the mouse gastrula is the first marker of the midbrain–hindbrain region. To address roles played by transcription factors in the process of neural plate pattern formation and to facilitate gain-of-function approaches in the study of midbrain–hindbrain and cerebellar developmen...
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Published in: | Brain research. Developmental brain research 1999-10, Vol.117 (1), p.99-108 |
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Main Authors: | , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | Expression of
Pax-2 in the mouse gastrula is the first marker of the midbrain–hindbrain region. To address roles played by transcription factors in the process of neural plate pattern formation and to facilitate gain-of-function approaches in the study of midbrain–hindbrain and cerebellar development, we characterized regulatory sequences at the
Pax-2 locus using an in vivo transgenic mouse reporter assay. An 8.5 kb fragment of genomic DNA located upstream of
Pax-2 directed
lacZ expression prior to neurulation (7.5 days post-coitum, dpc) in a region fated to become midbrain and hindbrain, and subsequently in developing neuroepithelium. While similar to the pattern of
Pax-2 expression, reporter gene activity extended beyond the boundaries of
Pax-2 expression, most probably reflecting purdurance of β-galactosidase activity and an absence of DNA sequences that restrict
Pax-2 expression to rhombomere 1 by 9.5 dpc. In the fetal and neonatal brain,
Pax-2-lacZ activity was confined largely to Purkinje cells and the external granule cell layer (EGL) of the cerebellum. A 4 kb regulatory element, in contrast, initiated neural expression at 8.25 dpc in the anterior hindbrain, but recapitulated all later aspects of
Pax-2-lacZ activity observed with the larger transgene. These results indicate the presence of regulatory sequences upstream of the
Pax-2 locus capable of directing gene expression in the developing midbrain, first rhombomere of the hindbrain, and its principal derivative, the cerebellum. Successful misexpression of
Sonic hedgehog demonstrates that
Pax-2 regulatory sequences should prove generally useful for transgenic gain-of-function approaches in mice. |
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ISSN: | 0165-3806 |
DOI: | 10.1016/S0165-3806(99)00104-2 |