This page contains a brief summary of my past (published) research. Consider it my personal C.V. for my scientific / academic carreer.
Mammalian Par3 Regulates Progenitor Cell Asymmetric Division via Notch Signaling in the Developing Neocortex
During brain development in the mouse, radial glial cells act as stem cells that give rise to most excitatory neurons in the adult cerebral cortex. During "peak neurogenesis", the period during embryo development where most neurons are formed, radial glial cells divide predominantly "asymmetrically", i.e. the two daughter cells are different: one will be another radial glial cells (which will then undergo the same process again), and the other will be either a transit-amplifying cell (a committed neuronal precursor that will divide to become two neurons) or a neuron.
© Elsevier press
This publication addresses the fundamental question of what proteins in these stem cells regulate asymmetric division of radial glial cells - i.e. what makes it possible that these two daughter cells, which both came from one single parent cell - are so fundamentally different. We found that:
- the mPar3 protein is asymmetrically localized in radial glial cells that are in mitosis (i.e. " currently dividing");
- Disruption of mPar3 asymmetry, either by "knock-down" (removal) or "overexpression", disrupted asymmetric cell division of radial glial cells;
- mPar3 activates (and is required for activation of) the Notch signaling pathway in radial glial cells, and this is required for mPar3 to regulate cell fate. Activation / regulation of Notch is interesting because it has been studied extensively by other scientists already;
- Regulation of the proliferative Notch signaling pathway by mPar3 in radial glial cells depends on its inhibition of the Notch inhibitors Numb and Numblike. These inhibitors are interesting because they, too, have been studied extensively by other scientists already.
Together, these results suggest that mPar3 regulates asymmetric division of radial glial cells by differentially manipulating the Numb / Notch signaling pathway in future daughter cells:
- In the daughter cell that inherits mPar3, mPar3 will block Numb, thereby preventing Numb from inhibiting Notch. Therefore, this cell will remain as a radial glial cell (a "stem cell");
- In the daughter cell that is devoid of mPar3, Numb will inhibit the proliferative Notch signaling pathway. Therefore, this cell will "differentiate", i.e. it will become a transit-amplifying cell or a neuron.