A “Deep Homology” of vertebrate external genitalia [with video]

The morphological evolution of external genitalia and limbs is considered an essential adaptation to a terrestrial lifestyle, once vertebrates started to conquer land. Surprisingly, we find that the developmental origin of genitalia varies considerably between extant vertebrate species, yet the inductive signals and ensuing gene regulatory networks during their organogenesis seem remarkably conserved.

HFSP Long-Term Fellow Patrick Tschopp and colleagues
authored on Mon, 01 December 2014

The embryonic development of vertebrate external genitalia and limbs relies on surprisingly similar gene regulatory networks. Based on this, as well as their adaptive value in a terrestrial environment, it had been speculated in the past that these two structures could have co-evolved together. We investigated this potential interrelation between the two organs in mice, chicken and squamates (lizards and snakes), which show progressive loss of limbs, yet maintain their paired external genitalia – the so-called hemipenis.

When looking at developing embryos of the various species, it immediately struck us that the squamate genitalia were at the same anterior-posterior position as the hindlimb. In contrast, the mouse counterpart was found in a more posterior position, towards the tailbud (see video below).

Figure: Python embryo at 11 days after oviposition (egg-laying). The right hemipenis (genitalia) bud and vestigial limb-bud can be seen near the tail end of the embryo, in the center of the tail "spiral" (two white "blobs").

This shift of the developing genitalia into the hind limb-field of squamates is paralleled by an equal transposition of the cloaca. This embryonic structure of the terminal gut tube is known to secrete signaling molecules important for genitalia outgrowth in mice and chicken. Lineage tracing experiments using GFP-expressing lentiviruses revealed that this repositioning indeed results in distinct cellular populations being recruited for genitalia development in the different species: while mouse external genitalia have their developmental origin mostly in the tailbud, the lizard hemipenis shares an embryonic lineage with the limb. It is a shared developmental trajectory, such as this, between the two organs, limbs and genitalia, that could help to explain the observed similarities in their gene regulatory networks, as demonstrated by our comparative RNA-seq transcriptomic analyses of the two structures in both lizards and mice.

Furthermore, grafting experiments suggested the conserved ability of different mesenchymal cells to respond to the inductive signals of the cloaca. Based on this, we hypothesized that a limb-derived developmental origin might represent the ancestral condition for the appearance of vertebrate external genitalia. Thus, while our study reveals that vertebrate external genitalia cannot be considered strictly homologous, they seem to share a “Deep Homology” - i.e. they rely on the same inductive signaling source, the cloaca, and respond with similar gene regulatory networks that might have become encoded in the genome when genitalia and limbs still developed from the same cellular source.

 

Reference

A relative shift in cloacal location repositions external genitalia in amniote evolution.Tschopp P, Sherratt E, Sanger TJ, Groner AC, Aspiras AC, Hu JK, Pourquié O, Gros J, Tabin CJ. Nature. 2014 Nov 5. doi: 10.1038/nature13819.

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