Research has suggested parallels in the development of fins and digits among different species. Specifically, the absence of certain hox genes appears to hinder the formation of fin rays in fish, indicating that digits may have evolved through modifications to an existing genetic framework initially designed for fin development.
However, a collaborative study involving US and French scientists revealed a more complex picture regarding the regulation of hox genes associated with limb formation. The hox gene clusters contain two essential pieces of regulatory DNA that influence gene activity—one located upstream and the other downstream of the gene clusters. Notably, in vertebrates, critical regulatory elements for one hox cluster reside upstream. When researchers deleted this segment, it resulted in complete inactivity of the cluster’s genes in the limb areas responsible for digit formation.
Different mechanisms at play
The research team decided to examine the equivalent regulatory region in zebrafish employing the gene-editing technology CRISPR. Contrary to expectations, the deletion of this specific area, which led to hox gene inactivity concerning digits in mice, had minimal impact in fish. While there was a slight decrease in hox gene activity, the genes remained operational at the correct times and locations necessary for digit formation. This suggests that, despite similar gene activity, the underlying mechanisms differ between fish and mice, implying that the hox gene functionalities concerning digits have evolved independently in the ray-finned fish and vertebrate lineages.
Curious about the role of the deleted regulatory DNA, researchers analyzed hox gene activity in both modified and unmodified fish. Notably, they identified that this regulatory element is significant in the developing cloaca, a multifunctional orifice in fish responsible for excretion and reproduction. Essentially, this structure serves a similar purpose to that of human anal openings.
