1. Guest lecturer: Kyle Belozerov
The Hippo Pathway
Guest lecturer: Kyle Belozerov
February 25, 2014

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

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

4. 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

5. 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): e doi: /journal.pbio

6. UAS/Gal4 binary system

7. 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): e doi: /journal.pbio

8. 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): e doi: /journal.pbio

9. 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): e doi: /journal.pbio

10. 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): e doi: /journal.pbio

11. 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): e doi: /journal.pbio