Maternal control of the formation of the polarized blastoderm epithelium in the Drosophila embryo
Zusammenfassung der Projektergebnisse
The molecular network regulating the establishment and maintenance of epithelial cell polarity is currently being investigated intensively. We are using Drosophila as model to study the genetic control of cell polarity in embryonic and adult epithelia. In Drosophila, epithelial polarity is initiated during cellularization of the syncytial blastoderm embryo. Our aim was to unravel molecular mechanisms governing establishment of cell polarity during cellularization. We focused our attention of maternal effect genes and discovered that drop out (dop) specifically affects membrane formation and polarized microtubule transport during cellularization. dop is allelic to argonaute2 (ago2), which encodes an essential protein component in RNA silencing. Our research demonstrated novel functions of Drosophila Argonaute proteins in cell formation and segment polarity. Cellularization occurs just after the maternal zygotic transition (MZT), during which maternal transcripts are degraded and zygotic transcription is initiated. We identified potential maternal mRNA targets of Ago2, which represent maternal transcripts that are degraded at MZT. The 3'UTRs of these transcripts are enriched for certain heptameric sequences, none of which represents a binding site for known miRNAs. In addition to our research on ago2, we have identified other genes required for cellularization. In a collaborative effort, we established a function of the guanine nucleotide exchange factor RhoGEF2 in the control of actin remodeling during furrow formation. In addition to Diaphanous as RhoA effector we found that mutation in another RhoA effector, Protein-Kinase N, also impair cellularization. The function of PKN was also studied in the follicle epithelium and found to be required for collective cell migration and coordinated cell constrictions. In conclusion the project revealed novel functions of Drosophila Argonaute genes providing evidence for the involvement of RNA silencing in the degradation of maternal transcripts at an decisive developmental transition, the MZT. Most importantly these results demonstrate that the degradation of certain subset of transcripts correlates with normal formation of cell polarity and membrane transport. The identification of specific functions of misregulated transcripts and their products will likely reveal novel insight into the regulation of the cell biology of cellularization.
Projektbezogene Publikationen (Auswahl)
- (2002). Germ Cell Migration: As Slow As Molasses. Curr. Biol. 12, R612-R614
Müller, H.-A.J.
- (2002). Mechanisms of Establishing Cell Polarity. Comments Theor. Biol. 7, 53-76
Müller, H.-A.J. and Bossinger, O.
- (2003). Control of Cleavage Cycles in Drosophila Embryos by Frühstart. Dev. Cell. 5, 285- 294
Grosshans, J., Müller, H.-A.J. and Wieschaus, E.
- (2003). Epithelial Polarity in Flies. More than just Crumbs. Dev. Cell 4, 1-3
Müller, H.-A.J.
- (2003). Molecular networks controlling epithelial polarity in development. Mech. Dev.. 120, 1231-1256
Müller, H.-A.J. and Bossinger, O.
- (2004). PKA-R1 regulation of PKA activity spatially restricts Oskar expression for Drosophila antero-posterior embryonic patterning. Development 131, 1401-1410
Yoshida, S., Müller, H.-A.J., Wodarz, A. and Ephrussi, A.
- (2005). RhoGEF2 and the formin Dia control the formation of the furrow canal by directed actin assembly during Drosophila cellularisation. Development. 132. 1009- 1020
Grosshans, J., Wenzl, C., Herz, H.M., Bartoszewski, S., Schnorrer, F., Vogt, N., Schwarz, H. and Müller, H.-A.J.
- (2006). Overlapping functions of Argonaute proteins in patterning and morphogenesis of Drosophila embryos. PLOS Genetics 2, 1224-1239
Meyer, W.J., Schreiber, S., Guo, Y., Volkmann, T., Weite, M.A., and Müller, H.-A.J.
