Another study on PCNT’s role in brain development

That new paper on PCNT’s role in microcephaly I just covered this afternoon has really sparked my interests. I have done a bit more digging around and came across another very recent paper, published about two weeks ago in Nature Genetics on PCNT’s role in inducing Seckel syndrome when it is nonfunctional. From OMIM, Seckel syndrome is a rare autosomal recessive disorder and it is characterized by growth retardation and microcephaly among other traits.

The paper, “Mutations in pericentrin cause Seckel syndrome with defective ATR-dependent DNA damage signaling” comes by way of researchers in the UK, Netherlands, and Saudi Arabia. From the abstract, you can get a feel for how important PCNT is,

“We now report that mutations in the gene encoding pericentrin (PCNT)—resulting in the loss of pericentrin from the centrosome, where it has key functions anchoring both structural and regulatory proteins—also cause Seckel syndrome. Furthermore, we find that cells of individuals with Seckel syndrome due to mutations in PCNT (PCNT-Seckel) have defects in ATR-dependent checkpoint signaling, providing the first evidence linking a structural centrosomal protein with DNA damage signaling. These findings also suggest that other known microcephaly genes implicated in either DNA repair responses or centrosomal function may act in common developmental pathways determining human brain and body size.”

Andrew Jackson of the Human Genetics Unit of the Medical Research Council, in Edinburgh is lead author. His team’s work along with Rauch’s research really help us see that any alteration in the mechanisms that drive the centrosome, such as in pericentrin, results in microcephaly. I summarized what PCNT encodes for, pericentrin, a protein that makes up the centrosome complex, in today’s previous post. The centrosome is a organelle that functions in regulating the cell cycle and cell division. What the centrosome really does is that it serves as an anchoring point to where microtublues are concentrated. The microtubules serve as ropes and poles which pull and push chromatids are aligned and then separated to help form two daughter cells. Should a component of the centrosome be flawed, say a messed up pericentrin protein because PCNT had mutations, then ultimately cell divsion, growth and development will be affected. Basically, the checkpoint wasn’t passed and mitosis won’t complete properly.

In the case of what we see in Homo floresiensis, we should always consider the possibility that such features are because of mutations in the development of the individuals. Many people were arguing this, they were saying Homo floresiensis‘ features were pathological. I think we’re just beginning to see how this could be, unraveling the functions of key developmental regulating genes.

3 thoughts on “Another study on PCNT’s role in brain development

  1. I just wonder if this condition can account for all of the other so-called primitive features of Homo floresiensis that are found fro example in the wrist and shoulder bones. Also the lengths of the limb bones don’t seem to match such an affliction either plus there was more than one specimen. How lucky or should I say unlucky, for us that a whole family would be found afflicted with this condition. Of course, you can use afflictions to eradicate the entire fossil record and for example attribute the grandiosity of sauropods to a glandular condition that only afflicted a few unfortunate individuals that we happened to uncover.

    Hopefully we’ll know more once the original research team gets back to the caves in Flores and to the other islands. Hard to believe, but their work was halted by the Indonesian government at one point further adding fuel to this mess. You have to wonder what Jacob’s role, the originator of the microcephalic theory, was in stopping the Australian team’s work and how much of his motivation was due to professional jealousy. Unfortunately, with Dr. Jacob’s recent death we may never know the entire story regarding his true motivations.

    Of course, I have a vested interest in this discovery, having written a speculative fiction novel called Flores Girl: The Children God Forgot on the recent fossil find. If you are interested, there is more on this ongoing controversy about Homo floresiensis at or catch the free Flores Girl podcast at

    Erik John Bertel

  2. My understanding regarding Primordial Dwarfism was that the entire body was proportionally dwarfed and that the affliction would not necessarily cause the proportional long limb bones seen in the Homo floresiensis specimens. In any case, more fossil specimens would a long way to dispelling this ongoing controversy. Of course, a live critter would be even better but I refuse to join the Sasquatch crowd.


  3. Erik,

    According to Rauch, who also published a recent paper on PCNT mutation (that I covered here), this condition does affect wrist bone development and can be attributed to the presence of deformation during skeletal development.


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