Fun Science Fact: Sonic Hedgehog
Yes, today’s post will be about Sonic Hedgehog. No, not “Sonic THE Hedgehog”, but Sonic Hedgehog, the gene and protein!
Yup, you read that right: there’s a gene that codes for a protein named after the famous video game character. You can color me just as surprised as you are.
Without further ado, and because I’m excited to tell you a little bit of what I found, let’s talk more about it!
Hedgehogs!
Why “Sonic Hedgehog?”
Well, the gene is one of the three Hedhegog (hh) genes. Without going into too much details, the hh genes are called like this because the loss of their function from a mutation results in the apparition of denticles, hedgehog-like spikes, on the embryo.
The “Sonic” part of the name was introduced after Robert Riddle, a postdoctoral fellow at the Tabin Lab, saw an ad for the game in a magazine. It’s been years since the scientific community has wanted to change it, but the name has stuck for so long already. Might as well keep it, if only to mention it as trivia at parties.
Roles and Functions
Okay, so we have Shh, a protein named after a video game character. Surely, there’s something else to say about it?
A Morphogen
Shh is a morphogen, aka “a substance whose non-uniform distribution governs the pattern of tissue development in the process of morphogenesis or pattern formation”.
Basically, it plays an important role in cell differenciation and proliferation, as well as body shaping, during the embryonic stage, and does so in a concentration gradient-dependent manner. We look the way we do in part thanks to it.
Shh is responsible for a bunch of areas, and a mutation in the gene can result in severe malformations. Let’s go over just a few of them.
Brain
We talk a lot about the brain on here. This time, though, it won’t be about dopamine, but the brain’s development in the womb.
Shh is responsible for the segmentation of the front part of the brain, known as “forebrain”. It divides it into two hemispheres: left and right. Specifically, it does so in the underside of the forebrain, creating the “ventral midline”.
So, what happens when this function is not fulfilled? A condition named nonsyndromic holoprosencephaly, where the brain fails to divide normally into two distinct hemispheres. While this is the main feature of the condition, it affects the face and head as well. As you can see in the pictures on the linked page, it can range from hypotelorism (eyes set close to each other) to more severe forms with cyclopia (one eye) and proboscis (tubular nasal structure).
Nonsyndromic holoprosencephaly comes with a set of other symptoms and disorders, such as intellectual disability, a dysfunctional pineal gland, and others which are listed on the linked page.
Eyes
We mentioned above that some severe cases of nonsyndromic holoprosencephaly come with cyclopia, which is a single eye instead of two. That is because Shh is also in charge of separating the eye field during the embryo’s development. The eye field is basically the “precursor” of the eyes; one structure that will later be divided and specialized into two distinct eyes.
Now, you know why Shh mutation may, in some cases, result in cyclopia. That’s not the only outcome, though.
Coloboma, missing eye tissue, is another possible outcome of a Sonic Hedgehog mutation. It shows as gaps in the eye structure. It can affect either or both eyes. It can affect the iris, retina, choroids (the blood vessels beneath the retina) or even the optic nerve. If it’s the latter, it will result in vision loss in part of the vision field. If it’s the iris, it will not result in vision loss. Finally, if it’s a large retinal or optic nerve coloboma, it will result in low vision, which cannot be fully corrected with glasses or lenses.
Another possible (and often associated) condition is microphtalmia. It is defined as “one or both eyeballs [being] abnormally small”. In some cases, they may seem to be completely missing. In microphtalmia, however, and unlike in anophtalmia, at least some tissue will remain. It may result in important vision loss.
Cancer
Visual pun aside, a dysregulation in the hedgehog signaling pathway (the chain of reactions regulating a cell function) is associated with cancer. It seems that too much of the Shh protein binds with PATCHED (PTC), which acts as a tumor suppressant. This binding mimics loss of PTC function (since, well, the coded protein is binded to Shh and can therefore not be used for something else). This suggests that Sonic Hedgehog deregulation may be involved in the development of cancers in humans.
(Maybe) Reversing Hair Loss
Every hair follicle we have had developed in the womb. After birth, no new follicle develops. This explains why injured skin cannot regrow hair. And yet…
A group of scientists experimented on a few lab mice (because that’s what scientists DO). The mice had injured skin, which in theory should not grow hair after scarring. The scientists activated the Sonic Hedgehog signaling in those mice’s skin, and lo and behold! The injured areas grew hair!
This could potentially mean gold in the area of significant skin injuries/scars and age-related hair loss. In order to avoid the development of cancer, a risk we mentioned in the previous section, the scientists only activated the pathway for the fibroblasts right below the skin.
The Bottom Line
There are more roles to the Shh gene and the protein it codes for, but I feel that the ones I mentioned above are enough. That, and I’m finishing this post less than 24 hours before it is scheduled to go online. Please cut me some slack.
I hope you liked this small “Fun Science Fact” type of post. I’m planning to do more in the future, because boy, is there a plethora of strange names in the field of biology.
Additional Resources
https://academic.oup.com/hmg/article/8/13/2479/651151
