What happens when Islet1 is knocked out in the lateral plate mesoderm?
Hindlimb field specification requires LIM-homeodomain transcription factor Islet1 in posterior lateral plate mesoderm. Islet1 promotes nuclear accumulation of beta-catenin activating beta-catenin pathway and directly drives Fgf10 expression initiating hindlimb bud. Early inactivation of Islet1 via conditional deletion in lateral plate leads to failure of Fgf10-Fgf8 feedback establishment selectively in hindlimb, resulting in complete hindlimb agenesis while forelimbs remain intact. It also regulates Hand2-Shh pathway posteriorly. Therefore Islet1 acts as hindlimb-specific initiator upstream of beta-catenin and represents missing regulatory link distinguishing hindlimb from forelimb.
Ref: Gilbert, Developmental Biology, 12th ed., Chapter 19: Islet1 in hindlimb initiation and beta-catenin activation pathway.