Damn those ugly facts!

Aw, I’m gutted.

In an undergrad developmental biology course that was otherwise not nearly as interesting as I’d expected to be, there were a few bits neat enough to make me (figuratively ;)) bounce up and down with joy. The differential cell adhesion hypothesis was one of these. It’s the idea that different types of cells in an embryo can sort themselves simply by basic physical forces depending on how sticky they are. If you mix cells with different stickiness, the ones that adhere more strongly to one another will clump on the inside. The great thing about this idea is that it’s a ridiculously simple explanation for the intricate cellular dance of gastrulation, which starts a homogeneous-looking ball of cells on its way to becoming a complex, multi-layered animal body.

If there’s one thing science should’ve taught me, it’s that simple ideas are usually too good to be the (complete) truth. And indeed, when Ninomiya et al. (2012) manipulated the stickiness of cells in frog embryos by changing the level of the “glue” protein C-cadherin, they were in for a little surprise. If differential cell adhesion was indeed responsible for cells organising into layers during gastrulation, then manipulating adhesion in the embryo should produce a visible gastrulation defect. But the only way this happened in this study was when the cells became so un-sticky that the tissue physically disintegrated. Altering general cadherin levels any less than that didn’t change a thing, and changing cadherin expression in just part of a single cell layer didn’t cause that layer to separate into two.

Interestingly, a soup of individual cells does sort itself into layers based on different stickiness. It just doesn’t happen in an intact embryo. So obviously, differential cell adhesion could do what it’s been theorised to do – but it’s not the (only) mechanism real live embryos use to organise themselves. The authors propose that cells in the embryo are (1) using adhesion/repulsion mechanisms other than cadherin to regulate their behaviour, (2) concentrating however much cadherin they possess where it’s most needed, compensating for an overall scarcity by changing the distribution of the protein. And probably cackling evilly to themselves. You thought you were clever, scientist? Well, screw you.

Reference:

Ninomiya H et al. (2012) Cadherin-dependent differential cell adhesion in Xenopus causes cell sorting in vitro but not in the embryo. Journal of Cell Science 125:1877-1883

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