LEF-1, a nuclear factor coordinating signaling inputs from wingless and decapentaplegic

Area of Science:

• Developmental biology
• Molecular genetics
• Signal transduction

Background:

• Wingless (wg) and decapentaplegic (dpp) signaling pathways are crucial for embryonic development in Drosophila.
• These pathways regulate the expression of key developmental genes, including homeotic genes like Ultrabithorax (Ubx).

Purpose of the Study:

• To identify and characterize the minimal wingless response sequence within the Ultrabithorax midgut enhancer.
• To investigate the role of the murine transcription factor LEF-1 in mediating wingless signaling and regulating Ubx expression.
• To understand how LEF-1 integrates multiple signaling inputs for enhancer activity.

Main Methods:

• Identification of a minimal wingless response sequence in the Ubx midgut enhancer.
• Analysis of LEF-1 binding to this sequence in a ternary complex with armadillo.
• Stable transformation assays to assess transcriptional stimulation by LEF-1.
• Overexpression studies of LEF-1 to observe developmental phenotypes.
• Investigation of LEF-1's dependence on dpp signaling for transcriptional activity.

Main Results:

• A minimal wingless response sequence in the Ultrabithorax enhancer was defined.
• The murine transcription factor LEF-1 binds to this sequence, forming a ternary complex with armadillo.
• Transcriptional stimulation by LEF-1 is dependent on armadillo and requires the decapentaplegic response sequence.
• Overexpression of LEF-1 mimics wingless hyperstimulation phenotypes and bypasses the need for wingless signaling.

Conclusions:

• LEF-1 acts as a critical mediator of wingless and decapentaplegic signaling in regulating Ultrabithorax expression.
• LEF-1 integrates multiple positional signals to coordinate enhancer activity.
• LEF-1 plays an architectural role in assembling multiprotein enhancer complexes during Drosophila development.