Polydactylism in domestic cats—often affectionately linked with Ernest Hemingway’s famous multitoed cats—is a well-known example of a genetic trait resulting from alterations in limb development regulation. Here’s an overview of the genetics behind this condition:
1. Autosomal Dominant Inheritance
- Inheritance Pattern:
In domestic cats, polydactylism is inherited in an autosomal dominant manner. This means that only one copy of the mutant allele is needed for a cat to display the trait. As a result, if one parent is polydactylous, there’s a high likelihood that some of its kittens will also have extra digits. - Variable Expressivity:
Although the trait is dominant, the number and placement of extra digits can vary considerably among affected cats. This variability—known as variable expressivity—means that while one cat might have a single extra toe on each paw, another might exhibit multiple extra digits or asymmetrical patterns.
2. The Role of Sonic Hedgehog (SHH) and Its Enhancer
- Sonic Hedgehog (SHH) in Limb Development:
SHH is a key signaling molecule during embryonic limb development. It is normally expressed in a specific region of the developing limb bud called the zone of polarizing activity (ZPA), which is situated on the posterior (little-finger) side of the limb. This localized expression is essential for the proper patterning and identity of digits. - The Zone of Polarizing Activity Regulatory Sequence (ZRS):
- Enhancer Function: The ZRS is a highly conserved regulatory element (an enhancer) that controls the precise expression of the SHH gene in the developing limb.
- Mutation Effects: In polydactylous cats, mutations in the ZRS lead to ectopic (misplaced) expression of SHH, particularly on the anterior (thumb or big toe) side of the limb bud. This aberrant expression results in the formation of extra digits, typically manifesting as preaxial polydactyly (extra digits on the front side of the paw).
3. Mechanistic Summary
- Mutation Location:
The critical mutations occur not in the coding region of the SHH gene itself but in its regulatory enhancer, the ZRS. This mutation disrupts the normal spatial control of SHH expression during limb development. - Outcome on Limb Formation:
The misregulation of SHH due to the ZRS mutation causes a broader or shifted zone of activity in the limb bud. As a consequence, extra digits form in regions where they normally would not, giving rise to the polydactylous phenotype. - Clinical and Phenotypic Observations:
While the extra digits do not typically impair the cats’ quality of life, their presence is a clear indicator of the underlying genetic alteration. The trait’s dominant inheritance ensures that it can be passed on through generations, with noticeable variation in the phenotype.
4. Conclusion
In summary, polydactylism in domestic cats is primarily caused by an autosomal dominant mutation in a regulatory enhancer (the ZRS) that controls the expression of the Sonic Hedgehog (SHH) gene during limb development. This mutation leads to ectopic expression of SHH in the limb bud, which in turn results in the formation of extra digits. The condition’s variable expressivity means that the exact number and position of these extra digits can differ from one cat to another, making each case of polydactylism somewhat unique.
Understanding this genetic mechanism not only illuminates the fascinating biology behind extra-toed cats but also provides broader insights into how precise regulatory control is essential for normal limb development in mammals.
