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Research identifies protein that regulates key 'fate' decision in cortical progenitor cells
Date:9/21/2012

hrough which DOCK7 expression affects the two essential but contrasting functions of RGCs. "Self-renewability of RGCs must be tightly balanced with differentiation for proper cortical development," says Van Aelst.

"The mechanism we discovered to be central in the determination of RGC fate, is called interkinetic nuclear migration, or INM," she continues, "and you can see it in action in the movies made by Drs. Wang and Yang."

In INM, an RGC cell nucleus visibly travels over the course of the cell cycle "upward" and "downward" between opposing sides of the apical-most region of the neuroepithelium, called the ventricular zone or VZ. Nuclei move away from the apical surface during the G1 phase, undergo S phase at a basal location in the VZ, and return to the apical surface during G2 to divide at the apical location.

It is DOCK7 that regulates this movement; in particular, the movement from the basal to apical location, the CSHL team has now demonstrated. On what appears to be the lower surface of the VZ, the apical surface, signals directing the RCG toward proliferation i.e., reproduction of other RGCs are dominant. On the upper or 'basal' side of the VZ, dominant signals coax the RGC to split into new intermediate progenitors or neurons.

Migration explained: DOCK7, TACC3 and centrosomes

"The cellular machinery that controls INM involves a protein complex of actin and myosin, called actomyosin, as well as microtubule-dependent systems," notes Dr. Wang. "We show how DOCK7 exerts its effects by antagonizing the microtubule growth-promoting function of a protein called TACC3." That protein, tellingly, is associated with the centrosome, the cellular organ that organizes microtubules, and regulates the growth of microtubules emanating from the centrosome, thereby coupling the centrosome and nucleus .

As Dr. Yang points out, DOCK7 acts by antagonizing the microtubule growth-promoting function of TACC3.
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Contact: Peter Tarr
tarr@cshl.edu
516-367-8455
Cold Spring Harbor Laboratory
Source:Eurekalert

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