Overexpression of connexin43 alters the mutant phenotype of midgestational wnt-1 null mice resulting in recovery of the midbrain and cerebellum.
Publication/Presentation Date
3-1-2005
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.
Volume
283
Issue
1
First Page
224
Last Page
238
ISSN
1552-4884
Published In/Presented At
Melloy, P. G., Kusnierczyk, M. K., Meyer, R. A., Lo, C. W., & Desmond, M. E. (2005). Overexpression of connexin43 alters the mutant phenotype of midgestational wnt-1 null mice resulting in recovery of the midbrain and cerebellum. The anatomical record. Part A, Discoveries in molecular, cellular, and evolutionary biology, 283(1), 224–238. https://doi.org/10.1002/ar.a.20158
Disciplines
Medicine and Health Sciences
PubMedID
15678491
Department(s)
Fellows and Residents
Document Type
Article