The FU gene and its possible protein isoforms

Area of Science:

• Genetics
• Molecular Biology
• Developmental Biology

Background:

• The FU gene is the human homolog of Drosophila fused, a positive regulator of Cubitus interruptus (Ci).
• FU is hypothesized to regulate human GLI transcription factors, which are key in Hedgehog signaling during development.
• Hedgehog signaling pathways are crucial for embryonic development and morphogenesis.

Purpose of the Study:

• To identify and characterize the FU gene and its genomic structure.
• To investigate the role of FU in human development, particularly in relation to Syndactyly type 1 (SD1).
• To explore the function of FU isoforms in regulating GLI transcription factors and Hedgehog signaling.

Main Methods:

• Gene identification and mapping to chromosome 2q35.
• Sequencing of the FU coding region in DNA from an SD1-affected family.
• Analysis of FU gene expression patterns across various human tissues using RT-PCR.
• Investigation of alternative splicing events and characterization of FU protein isoforms.
• Functional assays to assess the impact of FU isoforms on GLI1 and GLI2 activity.

Main Results:

• The FU gene was located on chromosome 2q35; its exon-intron organization was determined.
• No pathogenic mutations in the FU coding region were found in the SD1-linked family, though three SNPs were identified.
• FU is expressed in all examined tissues, with evidence of alternative splicing generating multiple transcript sizes and protein isoforms.
• One FU isoform enhanced GLI2 activity but had no effect on GLI1 activity or SUFU-mediated inhibition of GLI.

Conclusions:

• The FU gene and its genomic structure have been identified, positioning it as a candidate gene for SD1.
• Alternative splicing of FU transcripts leads to different protein isoforms with distinct regulatory potential.
• FU plays a role in Hedgehog signaling by enhancing GLI2 activity, implicating it in developmental processes regulated by this pathway.