Today in “Edna Explains Stuff That Actually, Really Happens in Their Mad Science Lab”: Retinoic acid beading.

I pulled these images from a 1985 paper* as they’re some of the clearest visualizations of a protocol that a couple volunteers in the lab are trying to get working. The protocol involves inserting a bead of retinoic acid into the limb bud of a chick embryo and allowing it to develop. Among others, you can get results like image “D” above (compared to the normal limb “A”): a direct mirror image of the digits - two “hands” on the same arm.

In the posterior part of the developing limb bud, there’s a region called the zone of polarizing activity (ZPA) that controls the development of the digits through various signalling pathways, most importantly the sonic hedgehog (shh) protein**. The ZPA particularly contributes to the differentiation of separate digits (antero-posterior development).

If a bead of retinoic acid is inserted into the anterior part of the limb bud, opposite the ZPA which is in the posterior part, it will essentially induce a secondary ZPA. The signalling of this second ZPA will create a second set of digits mirroring the first. Also notice that in image D, the distal (farthest from body) ends of the forearm both resemble an ulna rather than the normal ulna and radius.

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* Tickle, C. 1985. A Quantitative Analysis of the Effect of all-trans-Retinoic Acid on the Pattern of Chick Wing Development. Dev. Biol. 109, 82-95

** yes seriously it’s called that