Polarity in cell division: what frames thy fearful asymmetry?

Despite the considerable recent progress, many basic questions about the control of asymmetric division by polarity cues remain to be answered. For example: (1) What polarity cues are used to direct the successive asymmetric cell divisions within the NB lineage and the SOP lineage? In the case of SOPs in the notum, each division has a stereotyped orientation (Gho et al. 1999xGho, M, Bellaiche, Y, and Schweisguth, F. Development. 1999; 126: 3573–3584PubMedSee all ReferencesGho et al. 1999). Of those divisions, we know the polarity cue only for the first division, i.e., that planar polarity controls the division of SOP into a posterior IIa and an anterior IIb. What polarity cues are used to control the subsequent divisions? Is apical-basal polarity used to control the IIb division that gives rise to an apical and a basal daughter? What about the division that is at an oblique angle with respect to both apical-basal axis and the epithelial plane? How do the secondary and tertiary precursors keep track of the polarity information they need to orient their division? In situations in which the precursor seems to face more than one polarity cue, e.g., the SOP expresses both Inscuteable and Flamingo, how does it choose to use one of them? Is the unused cue reserved to be used in later divisions? Similar questions apply to the NB lineage. The first division of the NB into another NB and a GMC is controlled by apical-basal polarity, but what about later rounds of NB division given that the Bazooka and Inscuteable crescent disappears after anaphase of the first NB division? (2) What links the polarity cue to spindle orientation? (3) How does the polarity cue at one pole of the cell control the movement of the determinants and adapter molecules so that they form a crescent at the opposite pole? At present, this is probably the largest gap in our knowledge (for a discussion, see Lu et al. 1999axLu, B, Ackerman, L, Jan, L.Y, and Jan, Y.-N. Mol. Cell. 1999; 4: 883–891Abstract | Full Text | Full Text PDF | PubMedSee all ReferencesLu et al. 1999a). (4) How do the mechanisms for asymmetric cell division used in different organisms compare? Most of the molecules involved in the asymmetric cell divisions in the Drosophila nervous system have homologs in vertebrates and C. elegans (Figure 2Figure 2). Do they serve similar functions? It will be interesting to compare, for instance Drosophila embryonic neural precursor divisions with the first few cell divisions during C. elegans embryogenesis. Bazooka functions to link the apical-basal polarity from epithelium with NB polarity. In early C. elegans embryogenesis, there is no epithelial structure, so superficially the function of Par-3 appears to be different from Bazooka. However, once our knowledge is more complete, perhaps the similarity will become apparent. Perhaps the essential function of Par-3/Bazooka is to serve as an anchor to organize a special cortical domain and it is capable of responding to different polarity cues in different developmental systems.Several recent technical advances should accelerate the rate of progress. The various genome sequencing projects that are completed (yeast, worm, and fly) and soon to be completed (mouse and human) will greatly facilitate the identification of molecular components and the comparison of mechanisms used by different organisms. The increasing usage of GFP-tagged molecules allows monitoring of various aspects of asymmetric cell division events, such as spindle orientation (Kaltschmidt et al. 2000xKaltschmidt, J.A, Davidson, C.M, Brown, N.H, and Brand, A.H. Nat. Cell Biol. 2000; 2: 7–12Crossref | PubMed | Scopus (215)See all ReferencesKaltschmidt et al. 2000), movement of determinants or adapters (Lu et al. 1999bxLu, B, Usui, T, Uemura, T, Jan, L, and Jan, Y.-N. Curr. Biol. 1999; 9: 1247–1250Abstract | Full Text | Full Text PDF | PubMedSee all ReferencesLu et al. 1999b), and cell lineaging (Gho et al. 1999xGho, M, Bellaiche, Y, and Schweisguth, F. Development. 1999; 126: 3573–3584PubMedSee all ReferencesGho et al. 1999) in living organisms in real time. Such analysis will undoubtedly provide deeper insights into the process than experiments based on observations of fixed tissues.*To whom correspondence should be addressed (e-mail: ynjan@itsa.ucsf.edu).