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. Author manuscript; available in PMC: 2024 Oct 4.
Published in final edited form as: Reprod Toxicol. 2020 Nov 14;99:109–130. doi: 10.1016/j.reprotox.2020.10.014

Figure 4. ATRA signaling during development of the fetal appendicular skeleton.

Figure 4.

TOP: Mouse forelimb from early outgrowth (A, GD 9.5) to precartilage induction (B, GD10.5) to precartilage pattern (C, GD 11.5); corresponding stages in the hindlimb are delayed by a half day. The precartilage pattern is laid down in proximo-distal fashion for the stylopod (humerus, femur), zeugopod (radius-ulna, tibia-fibula), and autopod (digits of fore- and hind paw). BOTTOM: permissive ATRA signaling on proximo-distal patterning (from Uzkudun, Marcon et al. 2015). ATRA (from RALDH2) enters the proximal limb-bud and is degraded distally by CYP26B1 induced by FGF8; cells leaving the ATRA-free distal mesenchyme have positional values determining regional identity for stylopod (Meis), zeugopod (Hoxa11), and autopod (Hoxa13). Gradients represent two-signal model for ATRA and FGF8 signal inputs; a one-signal model (not shown) was also simulated wherein the time exposed to FGF8 alone determined regional identity.