Connexin50 is essential for normal postnatal lens cell proliferation.
OBJECTIVE
Connexin50 (Cx50) is absolutely essential for normal postnatal lens growth. Deletion of Cx50 or replacement with Cx46 by knockin resulted in smaller lenses containing fewer cells. To determine why Cx50-deficient lenses fail to grow normally, cell proliferation was assayed during the period of growth failure.


METHODS
Wild-type, Cx50-knockout, and Cx50KI46 mice were injected with 5'-bromo-2'-deoxyuridine (BrdU) and lenses were dissected and fixed after 1 hour or 24 hours. BrdU incorporation was visualized by immunocytochemical staining, and the mitotic index (MI) was determined between postnatal day (P)0 and P6. Levels of total ERK and phospo-ERK were determined by Western blot analysis.


RESULTS
On P2 to P3, wild-type lenses displayed a significantly increased MI not evident in knockout lenses, and knockin lenses only partially rescued the growth deficit. Reductions in the number of mitotic cells did not reflect a decrease in the rate of cell division and temporally correlated with reduction in lens mass. Levels of phosphorylated ERK1/2 were identical in wild-type and Cx50-deficient lens epithelia.


CONCLUSIONS
These results demonstrate that Cx50-mediated communication is necessary to achieve peak mitosis. In addition, they suggest a novel mitogenic role for gap junctional coupling that is connexin specific and independent of MAPK signaling.
Department of Physiology and Biophysics, State University of New York, Stony Brook, New York, 11794-8661, USA.
Caterina
C
Sellitto
Leping
L
Li
Thomas W
TW
White
D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development; D002455:Cell Division / Q000502:physiology; D017630:Connexins; D005136:Eye Proteins / Q000378:metabolism / Q000502:physiology*; D007908:Lens, Crystalline / Q000166:cytology* / Q000201:enzymology / Q000254:growth & development; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008938:Mitosis; D008940:Mitotic Index; D012016:Reference Values; D015398:Signal Transduction; D000099264:Connexin 50
D017630:Connexins; D005136:Eye Proteins; D020928:Mitogen-Activated Protein Kinases; D000099264:Connexin 50