Guest lecturer: Kyle Belozerov

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Presentation transcript:

Guest lecturer: Kyle Belozerov The Hippo Pathway Guest lecturer: Kyle Belozerov February 25, 2014 vbelozer@yorku.ca

What determines the size of an animal? Apoptosis Cell growth Cell proliferation Cell growth Cell proliferation Apoptosis Larger Cell growth Cell proliferation Apoptosis Smaller

The Hippo pathway, discovered in Drosophila in the early 2000’s Tissue size Planar Cell Polarity (PCP) Cell-fate determination Mitosis Pluripotency

The Drosophila Hippo pathway. The mammalian Hippo pathway. Par-1 Ser168 The mammalian Hippo pathway. Cyclin E DIAP1 Bantam Expanded Harvey K F , and Hariharan I K Cold Spring Harb Perspect Biol 2012;4:a011288 ©2012 by Cold Spring Harbor Laboratory Press

Figure 1. Par-1 P-element insertion lines enlarge organ size and promote Hpo pathway-responsive gene expression. Huang H-L, Wang S, Yin M-X, Dong L, et al. (2013) Par-1 Regulates Tissue Growth by Influencing Hippo Phosphorylation Status and Hippo-Salvador Association. PLoS Biol 11(8): e1001620. doi:10.1371/journal.pbio.1001620 http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1001620

UAS/Gal4 binary system

Figure 2. Overexpression of Par-1 triggers tissue overgrowth and inactivates Hpo signaling in a kinase-dependent manner. Huang H-L, Wang S, Yin M-X, Dong L, et al. (2013) Par-1 Regulates Tissue Growth by Influencing Hippo Phosphorylation Status and Hippo-Salvador Association. PLoS Biol 11(8): e1001620. doi:10.1371/journal.pbio.1001620 http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1001620

Figure 3. Inactivation of Par-1 reduces organ size and downregulates the Hpo pathway-responsive genes. Huang H-L, Wang S, Yin M-X, Dong L, et al. (2013) Par-1 Regulates Tissue Growth by Influencing Hippo Phosphorylation Status and Hippo-Salvador Association. PLoS Biol 11(8): e1001620. doi:10.1371/journal.pbio.1001620 http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1001620

Figure 4. Par-1 functionally interacts with the components of the Hpo pathway. Huang H-L, Wang S, Yin M-X, Dong L, et al. (2013) Par-1 Regulates Tissue Growth by Influencing Hippo Phosphorylation Status and Hippo-Salvador Association. PLoS Biol 11(8): e1001620. doi:10.1371/journal.pbio.1001620 http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1001620

Figure 5. Par-1 interacts with Hpo-Sav and regulates the phosphorylation of Hpo at Ser30. Huang H-L, Wang S, Yin M-X, Dong L, et al. (2013) Par-1 Regulates Tissue Growth by Influencing Hippo Phosphorylation Status and Hippo-Salvador Association. PLoS Biol 11(8): e1001620. doi:10.1371/journal.pbio.1001620 http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1001620

Figure 6. Par-1 disrupts the association of the Hpo-Sav complex in a kinase-dependent manner. Huang H-L, Wang S, Yin M-X, Dong L, et al. (2013) Par-1 Regulates Tissue Growth by Influencing Hippo Phosphorylation Status and Hippo-Salvador Association. PLoS Biol 11(8): e1001620. doi:10.1371/journal.pbio.1001620 http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1001620