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.