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On the Hippo signaling pathway

April 24, 2012

Here’s the abstract of a fairly new paper published by Cell Reports (“Premetazoan Origin of the Hippo Signaling Pathway”):

“Nonaggregative multicellularity requires strict control of cell number. The Hippo signaling pathway coordinates cell proliferation and apoptosis and is a central regulator of organ size in animals. Recent studies have shown the presence of key members of the Hippo pathway in nonbilaterian animals, but failed to identify this pathway outside Metazoa. Through comparative analyses of recently sequenced holozoan genomes, we show that Hippo pathway components, such as the kinases Hippo and Warts, the coactivator Yorkie, and the transcription factor Scalloped, were already present in the unicellular ancestors of animals. Remarkably, functional analysis of Hippo components of the amoeboid holozoan Capsaspora owczarzaki, performed in Drosophila melanogaster, demonstrate that the growth-regulatory activity of the Hippo pathway is conserved in this unicellular lineage. Our findings show that the Hippo pathway evolved well before the origin of Metazoa and highlight the importance of Hippo signaling as a key developmental mechanism predating the origin of Metazoa.”

This is interesting, especially from a front-loading perspective. The Hippo signaling pathway is an important developmental mechanism in Metazoa (animals), but all the core components of the Hippo signaling pathway have recently been found in unicellular Holozoa, which include the choanoflagellates.

A figure from the paper “Premetazoan Origin of the Hippo Signaling Pathway.”

Thus, the following Hippo pathway components have been found in unicellular organisms:

1) Hippo (kinase)

2) Warts (kinase)

3) Yorkie (coactivator)

4) Scalloped (transcription factor)

Specifically, these components have been found in Capsaspora owczarzaki. If you take a look at the above figure, you will see that this unicellular lineage is deeper-branching than the choanoflagellates. So, what are the Hippo components doing in unicellular organisms that don’t need them? This really isn’t expected from non-teleological evolution, but we’d expect this from front-loading. What’s very neat, too, is that the researchers discovered that these Hippo pathway components in Capsaspora owczarzaki can actually function in Drosophila. This is quite surprising from a non-telic viewpoint, because there’s no reason why these proteins in unicellular organisms should have the right sequence specificity to function in a very different multi-cellular organism like Drosophila. But it makes sense under the front-loading hypothesis, because we’d predict these proteins (more specifically, their ancestors) to be given a function that would conserve their sequence identity very well, such that when animals did appear on the scene, these components could be easily co-opted into a Metazoan role.

One Comment leave one →
  1. Blas permalink
    July 3, 2012 3:47 pm

    A tip for biologist that want to publish in Cell reports: Look for multicellular control genes in protozoans. Positive not expected result granted.

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