The pluripotent stem cells are capable to produce different types of progenies under different conditions. One of the major challenges of stem cell research is to understand the mechanism of differentiation of stem cell progenies. There have been increasing evidences suggesting that asymmetric division is involved in stem cell differentiation. We are using embryonic neural stem cells (neuroblasts) in Drosophila as the model system to study the stem cell asymmetric division.
In Drosophila embryonic central nervous system, neuroblasts divide to generate two non-identical progenies with distinct cell sizes: the large apical daughter cell remains as the neuroblast and the basal small cell is the ganglion mother cell, which will divide terminally to produce two neurons. Our study and others have shown that two groups of asymmetrically localized proteins are involved in neuroblast divisions. Baz, DaPKC, Par6, Insc, Pins and Gai form a complex and localize to the apical cortex of the dividing neuroblasts while cell fate determinants such as Pros/Mir and Numb/Pon localize to the basal cortex of the dividing neuroblast. At telophase, apical proteins remain cortically only in the future neuroblast and all basal proteins are exclusively sequestered into the ganglion mother cell. The apical complex functions to control and coordinate basal localization of cell fate determinants, mitotic spindle orientation and formation of asymmetric spindle.
The key molecules involved in asymmetric division are evolutionarily conserved and orthologs of all apical proteins, except Insc, have been identified in mammals. It has been shown that ectopically expressed mouse homolog of Pins can substitute Pins function and rescue pins phenotypes in fly embryos, suggesting a possibly conserved asymmetric division mechanism in mammals. We are extending our study on asymmetric divisions in mammalian neural stem cells.
Address: Drosophila Neurobiology Laboratory Institute of Molecular and Cell Biology Proteos 61 Biopolis Drive S(138673)
