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Dissection and Immunofluorescent Staining of Mushroom Body and Photoreceptor Neurons in Adult Drosophila melanogaster Brains
Published on: November 6, 2017
Novel roles for APC family members and Wingless/Wnt signaling during Drosophila brain development
Melissa A Hayden1, Kathryn Akong, Mark Peifer
1Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-3280, USA.
Abstract:
Construction of the brain is one of the most complex developmental challenges. Wnt signals shape all tissues, including the brain, and the tumor suppressor adenomatous polyposis coli (APC) is a key negative regulator of Wnt/Wingless (Wg) signaling. We carried out the first assessment of the role of APC proteins in brain development, simultaneously inactivating both APC1 and APC2 in clones of cells in the Drosophila larval optic lobe. We focused on the medulla, where epithelial neural progenitors shift from symmetric to asymmetric divisions across the lateral-medial axis. Loss of both APCs triggers dramatic defects in optic lobe development. Double mutant cells segregate from wild-type neighbors, while double mutant neurons form tangled axonal knots, suggesting changes in cell adhesion. Strikingly, phenotypes are graded along the anterior-posterior axis. Activation of Wg signaling downstream of APC mimics these phenotypes, a dominant-negative TCF blocks them, and a known Wg target, decapentaplegic, is activated in double mutant clones, strongly suggesting that the phenotypes result from activated Wg signaling. We also explored the roles of classic cadherins in differential adhesion. Finally, we propose a model suggesting that Wg signaling regulates fine scale cell fates along the anterior-posterior axis, in part by creating an adhesion gradient and consider possible alternate explanations for our observations.
Insights
Loss of adenomatous polyposis coli (APC) proteins in Drosophila optic lobe development disrupts brain formation. This study reveals APCs regulate Wnt/Wingless signaling, impacting cell adhesion and neural progenitor divisions.
Area of Science:
- Neuroscience
- Developmental Biology
- Genetics
Background:
- Brain development is a complex process influenced by signaling pathways.
- Adenomatous polyposis coli (APC) proteins are critical negative regulators of Wnt/Wingless (Wg) signaling.
- The role of APC proteins in brain development remains largely uncharacterized.
Purpose of the Study:
- To investigate the function of APC proteins in Drosophila brain development.
- To elucidate the role of APC in regulating Wnt/Wg signaling during optic lobe formation.
- To understand how APC loss affects neural progenitor division and cell adhesion.
Main Methods:
- Simultaneous inactivation of APC1 and APC2 in Drosophila larval optic lobe cell clones.
- Analysis of optic lobe morphology, cell division patterns, and axonal projections.
- Assessment of Wnt/Wg signaling pathway activation using downstream targets and dominant-negative inhibitors.
- Investigation of cadherin-mediated cell adhesion.
Main Results:
- Loss of both APC proteins leads to significant optic lobe developmental defects.
- Mutant cells exhibit altered cell adhesion and form tangled axonal structures.
- Phenotypes are graded along the anterior-posterior axis and linked to Wnt/Wg pathway activation.
- Decapentaplegic, a Wg target, is upregulated in APC-deficient clones.
Conclusions:
- APC proteins are essential for proper Drosophila brain development, likely through Wnt/Wg signaling regulation.
- Activated Wnt/Wg signaling in APC-deficient cells disrupts cell adhesion and neural patterning.
- Wg signaling may establish an adhesion gradient influencing cell fate determination along the anterior-posterior axis.
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