Ligand-independent activation of the Hedgehog pathway displays non-cell autonomous proliferation during eye development in Drosophila
Department of Molecular, Cell and Cancer Biology
Cancer Biology | Cell Biology | Developmental Biology | Genetics and Genomics | Molecular Biology
Deregulation of the Hedgehog (Hh) signaling pathway is associated with the development of human cancer including medullobastoma and basal cell carcinoma. Loss of Patched or activation of Smoothened in mouse models increases the occurrence of tumors. Likewise, in a Drosophila eye model, deregulated Hedgehog signaling causes overgrowth of eye and head tissues. Surprisingly, we show that cells with deregulated Hh signaling do not or only little contribute to the tissue overgrowth. Instead, they become more sensitive to apoptosis and may eventually be eliminated. Nevertheless, these mutant cells increase proliferation in the adjacent wild-type tissue, i.e., in a non-cell autonomous manner. This non-cell autonomous effect is position-dependent and restricted to mutant cells in the anterior portion of the eye. We also observe precocious non-cell autonomous differentiation in genetic mosaics with deregulated Hh signaling. Together, these non-cell autonomous growth and differentiation phenotypes in the Drosophila eye model reveal another strategy by which oncogenes may generate a supportive micro-environment for tumor growth.
DOI of Published Version
Mech Dev. 2012 Jul;129(5-8):98-108. doi: 10.1016/j.mod.2012.05.009. Epub 2012 Jun 5. Link to article on publisher's site
Mechanisms of development
Christiansen, Audrey E.; Ding, Tian; and Bergmann, Andreas, "Ligand-independent activation of the Hedgehog pathway displays non-cell autonomous proliferation during eye development in Drosophila" (2012). Molecular, Cell and Cancer Biology Publications. 72.