Connexin genes encode intercellular channels that help to coordinate development. In mice, the targeted deletion of different connexins produces disparate effects on ocular growth and differentiation in the lens, and the need for multiple channel subunits is poorly understood. Knockout of Cx46 causes a loss of homeostasis and cataracts. Deletion of Cx50 results in reduced ocular growth and cataracts. Targeted replacement of Cx50 with Cx46 by genetic knock-in corrected defects in cellular differentiation and prevented cataracts, but did not restore normal growth. These data show that intrinsic properties of Cx50 were required for cellular growth, whereas nonspecific restoration of communication by Cx46 maintained differentiation.