The temporal pattern of separation of the soft tissue between mouse digits was examined in an organ culture model system. Mouse limbs of different gestational age were cultured in vitro and the pattern of separation of the digits characterized. By gestational day 12.5 (E12.5) the limbs were committed to undergo separation of the soft tissue in the interdigital space when cultured in vitro. Prior to E12.5 digital separation did not occur and the limb tissues were not committed to this process. The addition of 10(-7) M retinoic acid (RA) to the media of E12 limbs was capable of inducing digit separation in the uncommitted limbs. Both the soft and hard tissue development of digits formed in vitro for either committed limbs or uncommitted limbs induced with RA was similar to the in vivo pattern.
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