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3. Overexpression of connexin43alters the mutant phenotype of midgestational wnt-1null mice resulting in recovery of the midbrain and cerebellum

Author

Melloy, Patricia G., Kusnierczyk, Michelle K., Meyer, Rita A., Lo, Cecilia W., and Desmond, Mary E.

Abstract

The midbrain-hindbrain (MHB) junction plays a key role in the patterning of the embryonic neural tube and the formation of brain structures such as the cerebellum. The mitogen wnt-1is critical for cerebellar development, as evidenced by the lack of MHB region and cerebellar formation in the wnt-1null embryo. We have generated wnt-1null embryos overexpressing the gap junction gene connexin43by crossing wnt-1null heterozygotes into the CMV43 mouse line. We have confirmed that these mice show an increase in gap junctional communication by dye coupling analysis. Two-thirds of wnt-1null CMV43+mouse embryos at E18.5 have a cerebellum. In addition, changes in the wnt-1null phenotype in mouse embryos overexpressing connexin43are observed as early as E9.5. At this stage, one-quarter of wnt-1null CMV43+embryos display extra or expanded tissue present at the MHB boundary (a wnt-1null enlarged phenotype). In situ hybridization studies conducted on these embryos have indicated no changes in the expression of embryonic brain positional markers in this region. We conclude from these studies that overexpression of the connexin43 gap junction restores cerebellar formation by compensating for the loss of wnt-1. © 2005 Wiley-Liss, Inc.

Published
2005
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4. Overexpression of connexin43 alters the mutant phenotype of midgestational wnt-1 null mice resulting in recovery of the midbrain and cerebellum.

Author

Melloy PG, Kusnierczyk MK, Meyer RA, Lo CW, and Desmond ME

Subjects
Animals, Cerebellum embryology, Connexin 43 biosynthesis, Female, Gestational Age, Image Processing, Computer-Assisted, Intercellular Signaling Peptides and Proteins biosynthesis, Male, Mesencephalon embryology, Mice, Mice, Knockout, Phenotype, Pregnancy, Wnt Proteins, Wnt1 Protein, Cerebellum metabolism, Connexin 43 genetics, Gap Junctions genetics, Gene Expression Regulation, Developmental, Intercellular Signaling Peptides and Proteins genetics, Mesencephalon metabolism
Abstract

The midbrain-hindbrain (MHB) junction plays a key role in the patterning of the embryonic neural tube and the formation of brain structures such as the cerebellum. The mitogen wnt-1 is critical for cerebellar development, as evidenced by the lack of MHB region and cerebellar formation in the wnt-1 null embryo. We have generated wnt-1 null embryos overexpressing the gap junction gene connexin43 by crossing wnt-1 null heterozygotes into the CMV43 mouse line. We have confirmed that these mice show an increase in gap junctional communication by dye coupling analysis. Two-thirds of wnt-1 null CMV43(+) mouse embryos at E18.5 have a cerebellum. In addition, changes in the wnt-1 null phenotype in mouse embryos overexpressing connexin43 are observed as early as E9.5. At this stage, one-quarter of wnt-1 null CMV43(+) embryos display extra or expanded tissue present at the MHB boundary (a wnt-1 null enlarged phenotype). In situ hybridization studies conducted on these embryos have indicated no changes in the expression of embryonic brain positional markers in this region. We conclude from these studies that overexpression of the connexin43 gap junction restores cerebellar formation by compensating for the loss of wnt-1.

Published
2005
Full Text
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