Related Experiment Video
Updated: Jan 8, 2026
Environmental Modulations of the Number of Midbrain Dopamine Neurons in Adult Mice
Published on: January 20, 2015
Proteolysis that is inhibited by hedgehog targets Cubitus interruptus protein to the nucleus and converts it to a
P Aza-Blanc1, F A Ramírez-Weber, M P Laget
1Department of Biochemistry and Biophysics, University of California, San Francisco 94143, USA.
Insights
Hedgehog signaling in Drosophila involves Cubitus interruptus (Ci) protein regulation. We identified a domain tethering Ci in the cytoplasm, and its cleavage allows nuclear translocation to regulate gene expression.
Area of Science:
- Developmental Biology
- Molecular Biology
- Genetics
Background:
- Cell-cell communication is crucial for tissue development.
- Hedgehog (Hh) signaling and Cubitus interruptus (Ci) protein are key in Drosophila anterior/posterior compartment border formation.
- Ci's role as a transcription factor is established, but its cytoplasmic localization presents a puzzle.
Purpose of the Study:
- To identify the mechanism regulating Ci localization and function.
- To elucidate how Hh signaling controls Ci activity at compartment borders.
- To understand the regulation of target gene expression in Drosophila development.
Main Methods:
- Protein domain identification
- Analysis of protein localization and cleavage
- Gene expression pattern analysis in Drosophila
Main Results:
- A novel domain tethering Ci to the cytoplasm was identified.
- Cleavage of Ci releases it from the cytoplasm, allowing nuclear translocation.
- Hedgehog signaling inhibits Ci proteolysis, influencing target gene expression.
Conclusions:
- Ci's cytoplasmic tethering and subsequent cleavage are critical for its function.
- Hh signaling modulates Ci activity by inhibiting its proteolysis.
- This regulatory mechanism explains the spatial patterns of gene expression at compartment borders.
Abstract:
Cell-cell communication at anterior/posterior compartment borders in Drosophila involves Hedgehog (Hh), a protein secreted by posterior cells, and Cubitus interruptus (Ci), a protein in the Hh response pathway in anterior cells. Although Ci is thought to have roles as a transcription factor repressing hh expression and activating target genes, it localizes in the cytoplasm of anterior cells. We report here the identification of a domain that tethers Ci in the cytoplasm and show that in some anterior cells, Ci is cleaved to generate a form that lacks the tethering domain. This form translocates to the nucleus where it represses hh and other target genes. Hh inhibits proteolysis of Ci, and we suggest that this inhibition leads to the observed patterns of expression of key target genes at the compartment border.
Related Concept Videos
09:21Phenotypic Profiling of Human Stem Cell-Derived Midbrain Dopaminergic Neurons
10:54Reliable Identification of Living Dopaminergic Neurons in Midbrain Cultures Using RNA Sequencing and TH-promoter-driven eGFP Expression
08:45Isolation, Culture and Long-Term Maintenance of Primary Mesencephalic Dopaminergic Neurons From Embryonic Rodent Brains
09:35Environmental Modulations of the Number of Midbrain Dopamine Neurons in Adult Mice
11:58Primary Culture of Mouse Dopaminergic Neurons
09:54Comprehensive Profiling of Dopamine Regulation in Substantia Nigra and Ventral Tegmental Area