1. In class today we discussed the big ideas that drive limb formation, the development of an arm or a leg in humans. Malformation of the limb can be an extremely detrimental condition to live with and a better understanding of the processes behind limb formation could eventually yield results that will help medical practitioners to prevent or treat malformed limbs in an optimal way. Many conditions that affect proper limb growth affect many other things, this is because the components that are necessary for limb formation are used in many other areas of development (for example, dwarfism doesn’t only reduce the height of someone, it has many other negative symptoms, such as apnea or hydrocephalus that must be addressed to stay as healthy as possible). For the proper growth of limbs, an extremely specific set of machines in our body must coordinate together almost perfectly. Our DNA, a long double helix chain with instructions along it, must be bound by these machines in the proper way at the proper time by the proper elements to yield the products that DNA encodes (which is often MORE machinery!). This dance requires that all the other machines do what they need to, whether that be to help the proper machine bind to the DNA at the right time or to remove it when its job is done. This binding and unbinding is the major means by which our cells accomplish their goals, such as dividing precisely millions of times to yield dextrous functional digits. These pieces of cellular machinery have simple functions, but there are so many different variations and flavours of them that when they are exposed to slightly different conditions they can yield dramatically different results that culminate into cellular activity; their orchestration and interactions between one another is the key to understand how something like fingers to play piano or write a paragraph for class can come from a lump of seemingly insignificant and underwhelming cells.

The hardest part was avoiding jargon by far. To find the proper words to express your point without jumping into science-language is its own test.

The ZPA regulatory sequence (ZRS) controls SHH expression for the developing limb and is an enhancer. Transplantation experiments yielded results that showed altered digit expression, and the same was detected with mice that had increased SHH expression beyond the normal ZPA. a second ZPA was even detected more anterior presumably in part due to the differential expression of SHH. The ZRS region has been shown to be influenced by point mutations as well. The 2.2 kilobase region it covers likely interacts with the promoter region or another regulatory site to increase expression.

One could test this experimentally by taking identical specimens and altering only that 2.2 kilobase region and measuring the SHH levels at and around the ZPA against each specimen. A correlational study could be to test the SHH expression in individuals with limb disorders and individuals without limb disorders at and around the ZPA and then compare the degree of malformation to the degree of differences in SHH expression in the tested areas. The observational / discovery-based science approach could be to comb through genetic data and see which regions of DNA seem to be correlated with limb malformation, and hope to see the ZRS region.