Fig. 4. Gas1^-/- limbs display defective cell proliferation in the AER and distal mesenchyme. In vivo BrdU labeling of control (con; A-C) and Gas1^-/- (-/-; A'-C') embryonic forelimbs. (A,A') At E10.5, BrdU-positive cells were markedly reduced in the mutant AER. (B,B') At E11.5, BrdU-positive cells were reduced in the region of distal mesenchyme (asterisk) in Gas1^-/-. At E12.5, control (C) and Gas1^-/- (C') have similar rates of cell proliferation in the interdigits between digits III/IV and IV/V, but reduced proliferation between digits II/III. Limbs were sectioned horizontally with the anterior at top. Note that the chondrogenic regions of digits III and IV have a lower rate of proliferation in the mutant (C'). (D) A table summarizing the BrdU counts of each stage.