Hedgehog signaling pathway

The hedgehog signalling pathway is a pathway based on three specific proteins called the hedgehog proteins.

The most well-studied of these proteins is the Sonic hedgehog protein, or SHH, which plays a key role in structuring the general shape of the body, called patterning.

During the third week of development, a solid rod of mesoderm called the notochord forms at the midline of the embryo.

The notochord is extremely important during early development because it helps influence how the embryo folds.

It also guides how the various tissues differentiate and develop so that the embryo ends up with two arms, two legs, and one head, instead of some other combination.

Groups of proteins in the notochord secrete proteins that guide this process.

These include Desert hedgehog protein (DHH), Indian hedgehog protein (IHH), and Sonic Hedgehog protein (SHH).

Desert and Indian Hedgehog protein were named first, and Sonic was named a bit later—if you played video games in the ‘90s, you’ll know that it’s named after the fast-moving rodent, Sonic the Hedgehog!

The Hedgehog proteins are ligands, meaning they’re molecules that move from one cell over to another and facilitate communication—like letters that one cell might send to another cell around the corner.

Early in development, the notochord sends all three Hedgehog proteins out to undifferentiated cells throughout the entire embryo.

When Sonic Hedgehog protein gets released, it slowly diffuses through the interstitial liquid and binds to a receptor called patched (ptc), which can be found on the cell membranes of embryonic cells.

The patched receptor inhibits the embryonic cell from differentiating, but Sonic Hedgehog protein inhibits patched, meaning it inhibits the inhibitor!

Without the inhibition usually imposed by patched, the embryonic cell starts to activate specific genes that allow it to differentiate.

But every embryonic cell doesn’t differentiate in the same way—some might activate genes that allow them to be part of a leg, whereas others might activate genes that allow them to be part of an ear.

The precise set of genes that get expressed in one cell versus another cell depends on how much Sonic Hedgehog protein reaches the embryonic cell, and how long the embryonic cell is exposed to Sonic Hedgehog protein.

One way to think about this is that it’s the cumulative dose of Sonic Hedgehog protein that determines which genes get expressed and, ultimately, what each embryonic cell turns into.

When Sonic Hedgehog protein is released by the notochord, it diffuses throughout the embryo, forming a concentration gradient.

To better visualize this, let’s look at a grid, and say each square in the grid is an embryonic cell.

The embryonic cells nearest to the notochord get exposed to a high dose of Sonic Hedgehog protein, while the embryonic cells furthest away are exposed to a lower dose of Sonic Hedgehog protein.