Why do baby neurons need LIS1?

This time I picked an "old" paper. It was published last year on JCB and describes the effects of knocking down Lis1 during brain development.

LIS1 RNA interference blocks neural stem cell division, morphogenesis, and motility at multiple stages.
Tsai JW, Chen Y, Kriegstein AR, Vallee RB.
J Cell Biol. 2005 Sep 12;170(6):935-45

Cortical neuron migrate from the ventricular region to the perifery of the brain during brain development. Cortical neurons originate from the division of radial glial cells. Prior to cell division, the nucleus from radial cells migrates, away from the ventricular region, then returns to the initial position. Only after this detour, known as nuclear oscilation, radial glial cells divide. The daugther cells migrate to the sub-ventrical zone where they stop and become multipolar. Then they start extending axonal processes, become bipolar, and resume migration.
Lis1 mutations originate Lyssencephaly. Pacients with this mutations have severe defects on brain development and die 1-2 years after birth. Lis1 mutations are thought to interfere with neuronal migration required for brain development.
In this paper, the authors provide clear evidence for a role of Lis1 in different stages of neuronal migration. They used a very powerfull technique (in utero electroporation) to introduce fluorescent siRNA or shRNA targeting Lis1 into cells at the ventricular region. Then they analised the position and shape of transfected cells, and most impressivelly, they followed neuronal migration in slices by timelapse microscopy, up to 18h.
Using these approached they show that Lis1 is required for nuclear oscilations and cell division in astral glial cells, bipolar migration and axonal extension.


At Monday, June 12, 2006, Blogger Claudi said...

Lis1 rings a bell, is this an actin binding protein? Do the authors propose a mechanism whereby Lis1 regulates neuronal migration?

At Wednesday, June 14, 2006, Blogger Evil Gomez said...

No, Lis1 does not bind actin, but it binds dynein, a microtubule motor. Mutations in NUDF, the Lis1 ortholog in Aspergillus nidulans originates the same phenotype (defect in nuclei position) as dynein mutations, suggesting that Lis1 mutations interfere with dynein activity. In the paper described in this post, the authors show that interfering with dynein originates a similar phenotype as lis1 siRNA. In neuronal migration, dynein activity may be important for the position of the centrosome in front of the nucleus and the characteristic saltatory movement of the centrosome and nucleus. Dynein may also have a role in movement of the nucleus towards the centrosome, although two papers published last year implicated myosin and actin in this nuclear movement.

Journal of Neuroscience 25 (24), 5691 (2005)
Proceedings of the National Academy of Sciences 102 (38), 13652 (2005)

At Thursday, July 20, 2006, Anonymous Tulula said...

Being ignorant about science, I have no idea what this post is about. But I wanted to thank Evil Gomez for leaving a lovely comment on my blog. Not quite sure what it said, b/c Dictionary.com mangled the translation, but I'm sure it was nice!

Have a lovely day,



Post a Comment

Links to this post:

Create a Link

<< Home