“The team at Johns Hopkins University of Medicine, in Baltimore, used lab mice that were genetically engineered to have extra copies of about half the genes found on human chromosome 21, leading to Down syndrome-like conditions such as smaller brains and difficulty learning to navigate a maze.

On the day the mice were born, scientists injected them with a small molecule known as a sonic hedgehog pathway agonist.”

sonic hedgehog pathway? who said playing video games never gets you anywhere ?

http://www.abc.net.au/news/2013-09-05/downs-syndrome-reversed-in-newborn-mice/4936412

Well, they had to improve upon the usual naming, like – MAP kinase kinase kinase kinase…

poikilotherm said:

Well, they had to improve upon the usual naming, like – MAP kinase kinase kinase kinase…

I’d love to name some of those things… it seems anything goes, you can use your own name or the name of your favourite cartoon character or, if it’s a particularly nasty something something, the name of your ex.

too bad I don’t have the science to back up all my naming skills.

Hedgehog signaling pathway

The Hedgehog signaling pathway is a signaling pathway that transmits information to embryonic cells required for proper development. Different parts of the embryo have different concentrations of hedgehog signaling proteins. The pathway also has roles in the adult. Diseases associated with the malfunction of this pathway include basal cell carcinoma.

The Hedgehog signaling pathway is one of the key regulators of animal development and is present in all bilaterians. The pathway takes its name from its polypeptide ligand, an intercellular signaling molecule called Hedgehog (Hh) found in fruit flies of the genus Drosophila. Hh is one of Drosophila’s segment polarity gene products, involved in establishing the basis of the fly body plan. The molecule remains important during later stages of embryogenesis and metamorphosis.

Mammals have three Hedgehog homologues, DHH, IHH, and SHH, of which Sonic is the best studied. The pathway is equally important during vertebrate embryonic development. In knockout mice lacking components of the pathway, the brain, skeleton, musculature, gastrointestinal tract and lungs fail to develop correctly. Recent studies point to the role of Hedgehog signaling in regulating adult stem cells involved in maintenance and regeneration of adult tissues. The pathway has also been implicated in the development of some cancers. Drugs that specifically target Hedgehog signaling to fight this disease are being actively developed by a number of pharmaceutical companies.

Discovery

In the 1970s, a fundamental problem in developmental biology was to understand how a relatively simple egg can give rise to a complex segmented body plan.

[…]

The Drosophila hedgehog (hh) gene was identified as one of several genes important for creating the differences between the anterior and posterior parts of individual body segments. The fly hh gene was independently cloned in 1992 by the labs of Jym Mohler, Philip Beachy, and Thomas B. Kornberg. Some hedgehog mutants result in abnormally-shaped embryos that are unusually short and stubby compared to wild type embryos. The function of the hedgehog segment polarity gene has been studied in terms of its influence on the normally polarized distribution of larval cuticular denticles as well as features on adult appendages such as legs and antennae. Rather than the normal pattern of denticles, hedgehog mutant larvae tend to have “solid lawns” of denticles (Figure 1). The appearance of the stubby and “hairy” larvae inspired the name ‘hedgehog’.

Sonic hedgehog

Sonic hedgehog is a protein that in humans is encoded by the SHH (sonic hedgehog) gene.

Sonic hedgehog is one of three proteins in the mammalian signaling pathway family called hedgehog, the others being desert hedgehog (DHH) and Indian hedgehog (IHH). SHH is the best studied ligand of the hedgehog signaling pathway. It plays a key role in regulating vertebrate organogenesis, such as in the growth of digits on limbs and organization of the brain. Sonic hedgehog is the best established example of a morphogen as defined by Lewis Wolpert’s French flag model—a molecule that diffuses to form a concentration gradient and has different effects on the cells of the developing embryo depending on its concentration. SHH remains important in the adult. It controls cell division of adult stem cells and has been implicated in development of some cancers.

[…]

Investigations aimed at finding a hedgehog equivalent in vertebrates by Philip Ingham, Andrew P. McMahon, and Clifford J. Tabin, revealed three homologous genes. Two of these, Desert hedgehog and Indian hedgehog, were named for species of hedgehogs, while sonic hedgehog was named after Sega’s video game character Sonic the Hedgehog.

[…]

Criticism of the name

Some clinicians and scientists criticize giving genes frivolous, whimsical, or quirky names, calling it inappropriate that patients with “a serious illness or disability are told that they or their child have a mutation in a gene such as sonic hedgehog.”

Kinda off topic but I have never understood why those affected by this disease always have the same facial features. Why does it do this?

It happens in many genetic diseases, and pretty much all that relate to gene dosage (ie too many or too few copies of a gene or genes) have characteristic facies. Relates to the genes they have too many or not enough of. With Down syndrome in particular, because it’s so common, particular features have been mapped to either individual genes on chromosome 21, or at least regions.

OCDC said:

It happens in many genetic diseases, and pretty much all that relate to gene dosage (ie too many or too few copies of a gene or genes) have characteristic facies. Relates to the genes they have too many or not enough of. With Down syndrome in particular, because it’s so common, particular features have been mapped to either individual genes on chromosome 21, or at least regions.

Thank you for that. So it is basically the affected genes doing the same thing in everyone affected?

Yep.

“Some clinicians and scientists criticize giving genes frivolous, whimsical, or quirky names, calling it inappropriate that patients with “a serious illness or disability are told that they or their child have a mutation in a gene such as sonic hedgehog.””

boo

Arts said:

“Some clinicians and scientists criticize giving genes frivolous, whimsical, or quirky names, calling it inappropriate that patients with “a serious illness or disability are told that they or their child have a mutation in a gene such as sonic hedgehog.””

boo

IKR

I mean, what’s wrong with cheap date or dickkopf?

They’re being insensitive to people who have had a humourectomy.

Obviousman said:

OCDC said:

It happens in many genetic diseases, and pretty much all that relate to gene dosage (ie too many or too few copies of a gene or genes) have characteristic facies. Relates to the genes they have too many or not enough of. With Down syndrome in particular, because it’s so common, particular features have been mapped to either individual genes on chromosome 21, or at least regions.

Thank you for that. So it is basically the affected genes doing the same thing in everyone affected?

Yes. I had a child with partial trisomy 14 (Down syndrome is partial trisomy 21). She had similar facial features. Down syndrome is peculiar in that the deviation in appearance is quite strong while at the same time mental retardation is quite mild. In other chromosomal disorders people with that level of appearance would be much more severely mentally and physically retarded. On rare occasions (three times) I have noticed people of normal intelligence with similar facial features.

Reversing Down syndrome by simply using a “sonic hedgehog pathway agonist” is startling. It can’t be the whole story. Because Down syndrome involves trisomy there are three copies of many genes instead of the usual two. My thought had been that shutting down exactly 1/3 of the action of a large number of different genes without shutting down the remaining 2/3 would be an impossible task.

> “Most people with Down syndrome have a cerebellum that’s about 60 per cent of the normal size. We were able to completely normalise growth of the cerebellum through adulthood with that single injection. The injection also led to unexpected benefits in learning and memory, normally handled by a different part of the brain known as the hippocampus. Researchers found that the treated mice did as well as normal mice on a test of locating a water platform while in a swimming maze.”

So I’m surprised that they tried it and totally floored by the fact that it worked.