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   square14_green.gif   research summary

 


 

 

 

 

Most animal cells are asymmetrically polarized and exhibitapical-basal polarity.  Even non-polarized cells such as fibroblasts and single cells such as yeasts show apical-basal polarity, suggesting that some intrinsic factors in cells determine the cell polarity.  The cell polarity can be obtained by delivery of post-Golgi vesicles precisely to the specified membrane addition site, and this process is essential not only for the establishment of cell polarity but also for supplying the membrane lipids and proteins to the proliferating cells. Thus, disruption in this process results in loss of cell polarity as well as disruption in cell proliferation, two of the hallmarks of cancer cells. 

    We became interested in studying how cell growth and cell polarity are connected since I had discovered the link between Discs-Large (Dlg) and plasma membrane formation.  dlg has been considered a tumor suppressor gene in flies, because loss of dlg function in the fly results in overgrowth of proliferating diploid cells in the larval imaginal discs.  A series of recent reports have also demonstrated that Dlg plays a major role in establishing cell polarity.  Consistent with these reports, we have found that interaction between Dlg and Van Gogh (Vang)/Strabismus (Stbm) is linked to the plasma membrane formation.  Although the biochemical function of Stbm is still unknown, it is one of Frizzled (Fz) pathway proteins including Frizzled (Fz), Dishevelled (Dsh) and Prickle (Pk) that are involved in tissue polarity, convergent extension during vertebrate development, and inner ear hair development. 

              Despite our knowledge on these polarity proteins, it is still mostly unknown how these proteins work together to achieve cell and tissue polarity.  Several interesting reports provide an important clue that these polarity proteins may be involved in regulating microtubules.  This idea makes a great deal of sense because microtubules act as highways for delivering vesicles to the right place in the plasma membrane, and regulation of microtubule formation and dynamics seems to be the best target for the polarity proteins.  Consistent with this idea, our data suggest that Dlg and Stbm are essential for the formation and maintenance of microtubules.  We are currently testing whether other polarity proteins are also involved in regulating microtubule structure and dynamics.

 

             We are also interested in studying fly eye development.  In Drosophila, adult structures are developed from the primordia in the form of imaginal discs that are sac-like structures with continuous epithelial cell layers.  Unlike other primordia for wings or legs that are derived from a single embryonic segment, eye primordium is present in the eye-antenna disc that is composed of seven embryonic segments.  Due to this complexity and the extremely small size of the eye-antenna disc during early larval stage, the link between embryonic eye precursor and larval eye-antenna discs is largely unknown.  Despite these difficulties, we found that Hedgehog (Hh) can either promote or suppress of the growth of the various cell types in eye-antenna discs: without Hh, dorsal domain showed cell death, while the ventral domain exhibited over-proliferation.  Wingless (Wg) and Decapentaplegic (Dpp) also exhibited various effects on growth.

         

             Another interesting finding is the potential involvement of a sensory nerve in the formation of ventral domain in eye-antenna disc.  We are very excited to further examine the importance of this sensory nerve on the formation of eye primordium.  This study is directly relevant to the vertebrate eye and will help understand the evolutionary link between fly and vertebrate eyes.

 

 

 

 

 

 

 

 

 

 

 

     

 

 

 


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