In chapter three, Shubin talks about the function of Sonic hedgehog, which acts in the ZPA to control how the digits formed, and what they would look like (for example, look at your hand--the formation of the pinky and thumb, their length and distance from each other, is controlled mainly by the ZPA). Shubin also briefly discusses how if "things go wrong with Sonic hedgehog, the hand ends up looking like a broad paddle with as many as twelve fingers that all look alike" (53). What are some of these possible errors that would throw off the formation of digits, and how does this happen? Have there been past experiments on how we can prevent this from happening? Explain with specific examples.
Kathy Li, kathy2132@gmail.com
As Shubin explained, ZPA (the zone of polarizing activity) releases a chemical signal to tell the body where to grow certain kinds of digits (50-51). The Sonic hedgehog gene (Shh) is expressed in the ZPA, and this gene is the reason for the difference in the types of digits you see created. The concentration of the Shh protein helps convey positional information to indicate to the body where the posterior and anterior sides of a limb are; as Shh is farther away from ZPA, the concentration decreases, and more anterior digits develop (Campbell 1043). In essence, Shh is the reason for why digit formation works so well and therefore any problems that arise in its production or expression can result in defective digit formation.
ReplyDeleteIt has been shown that changing expression of the Shh gene can result in a condition called polydactyly (extra digits) in mice, as well as other skeletal defects (http://hdl.handle.net/10504/5647). If the gene is regulated badly, concentration of the protein may change, cause higher or lower production of digits. In fact, Shh can be thought of as the mechanism by which the body controls the amount of digits that are produced (http://www.physorg.com/news187378839.html), as the concentrations are precisely controlled to create the correct digits. Errors such as mis-expression of the Shh gene can be caused by inhibitors such as cyclopamine in urodele amphibians (e.g. salamanders), an example of an experiment investigating the affects of Shh inhibition on digit formation; in fact, this change in expression is analogous to how urodele amphibians, as time went on, developed natural variation in digit number (http://www.ncbi.nlm.nih.gov/pubmed/17117438). Cyclopamine can also cause defects in humans, as it causes holoprosencephaly (prevention of the brain of a fetus from dividing into two lobes) and cyclopia, demonstrating how the hedgehog pathway not only has importance in limb development but in development all over the body. Ethanol has long been known to cause limb development defects, but recently it has actually been connected to problems in Shh; it was found that ethanol directly reduces expression of Shh in the ZPA (http://onlinelibrary.wiley.com/doi/10.1002/bdra.20019/abstract). That experiment suggests that one method of preventing digit formation defects is not ingesting ethanol during gestation, preventing the errors that can occur because of faulty Shh expression. In general, any inhibitor of Shh expression will cause errors in formation of digits, and create problems like polydactyly when Shh is not controlled correctly.
Eugene Bulkin (doubleaw002@gmail.com)
prof premraj pushpakaran writes -- 2018 marks the 100th birth year of Edward Butts Lewis!!!
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