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Tow (Target of Wingless), a novel repressor of the Hedgehog pathway in Drosophila

Katie L Ayers1, Ralph Rodriguez, Armel Gallet

  • 1Institute of Developmental Biology and Cancer Research, CNRS UMR 6543, Centre de Biochimie, Université de Nice-Sophia Antipolis, Parc Valrose, 06108 Nice Cedex 2, France.

Developmental Biology
|March 17, 2009
PubMed

Insights

Researchers identified Target of Wingless (Tow) as a novel repressor of the Hedgehog (Hh) signalling pathway. Tow acts upstream of Smoothened (Smo) in Hh receiving cells, impacting development and potentially disease.

Area of Science:

  • Developmental Biology
  • Molecular Biology
  • Genetics

Background:

  • Hedgehog (Hh) signalling is vital for tissue development and patterning.
  • Dysregulation of Hh signalling is linked to developmental abnormalities and cancer.
  • The precise mechanism of repressing the Hh pathway activator Smoothened (Smo) in the absence of Hh remains incompletely understood.

Purpose of the Study:

  • To identify novel regulators of the Hedgehog (Hh) signalling pathway.
  • To elucidate the role of Target of Wingless (Tow) in Hh signal transduction.
  • To investigate the interaction of Tow with other components of the Hh pathway, such as Patched (Ptc) and Smoothened (Smo).

Main Methods:

  • Genetic analysis in Drosophila melanogaster.
  • Overexpression studies of the novel repressor Target of Wingless (Tow).
  • Analysis of lipophorin accumulation in wing discs.

Main Results:

  • Target of Wingless (Tow), a novel protein, acts as a repressor in Hh receiving cells.
  • Tow's repression occurs upstream or at the level of Smoothened (Smo) and downstream of Patched (Ptc).
  • Overexpression of Tow leads to lipophorin accumulation, similar to Patched (Ptc), and loss of tow enhances ptc alleles.

Conclusions:

  • Tow is identified as a significant novel regulator of the Hh pathway in the Drosophila wing imaginal disc.
  • Tow's function may provide insights into the mechanism by which Patched (Ptc) represses Smoothened (Smo).
  • Tow's role in lipophorin internalisation suggests a link between Ptc-mediated repression and cellular processes.

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