Point mutations in a distant sonic hedgehog cis-regulator generate a variable regulatoryoutput responsible for preaxial polydactyly

Laura A. Lettice, Alison E. Hill, Paul S. Devenney and Robert E. Hill

Polydactyly

Sonic hedgehog is a morphogen that plays a key role in regulating vertebrate organogenesis, such as in the growth of digits on limbs and organization of the brain

What’s the Hypothesis?

Which are the predictions and methods?

ZRS mutations cause polydactyly in cats and they generate a plastic

regulatory response

GENE REGULATION

Are there mutations in the ZRS that cause polydactyly in domestic cats?

Is Human preaxial polydactyly (PPD) associated point mutations generate a plastic regulatory response?

Is the cat Hw mutation forelimb specific? Do neighboring mutations have different activities?

Interesting quotes:

“The unlikely scenario is that each mutation causes ectopic expression by its own unique mechanism and therefore, we predict it is more likely that the point mutations, perhaps by a number of different routes, affect a general property of the cis-regulator.”

“In addition, the basis for differences between species may be changes at the level of gene regulation. In accord, our analysis showed that point mutations in a key developmentalcis-regulator can result in additional skeletal elements supporting the notion that small regulatory changes can have profound affects on the morphology of the animal.”