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let-756, a C. elegans fgf essential for worm development
R Roubin1, K Naert, C Popovici
1Laboratoire d'Oncologie Moléculaire, U119 Inserm, Marseille, France.
Abstract:
In vertebrates, Fibroblast Growth Factors (FGFs) and their receptors are involved in various developmental and pathological processes, including neoplasia. The number of FGFs and their large range of activities have made the understanding of their precise functions difficult. Investigating their biology in other species might be enlightening. A sequence encoding a putative protein presenting 30-40% identity with the conserved core of vertebrate FGFs has been identified by the C. elegans sequencing consortium. We show here that this gene is transcribed and encodes a putative protein of 425 amino acids (aa). The gene is expressed at all stages of development beyond late embryogenesis, peaking at the larval stages. Loss-of-function mutants of the let-756 gene are rescued by the wild type fgf gene in germline transformation experiments. Two partial loss-of-function alleles, s2613 and s2809, have a mutation that replaces aa 317 by a stop. The truncated protein retains the FGF core but lacks a C-termins portion. These worms are small and develop slowly into clear and scrawny, yet viable and fertile adults. A third allele, s2887, is inactivated by an inversion that disrupts the first exon. It causes a developmental arrest early in the larval stages. Thus, in contrast to the other nematode fgf gene egl-17, let-756/fgf is essential for worm development.
Insights
The C. elegans let-756 gene encodes a Fibroblast Growth Factor (FGF) essential for larval development. Loss-of-function mutations cause developmental delays or arrest, highlighting its crucial role in worm growth.
Area of Science:
- Developmental Biology
- Genetics
- Molecular Biology
Background:
- Fibroblast Growth Factors (FGFs) are vital in vertebrate development and disease.
- Understanding FGF functions is challenging due to their numerous roles.
- Studying FGFs in other species like C. elegans offers insights.
Purpose of the Study:
- To characterize the function of a putative FGF gene (let-756) in C. elegans.
- To determine the expression pattern and essentiality of let-756 during development.
Main Methods:
- Sequence analysis of the putative FGF gene.
- Analysis of gene transcription and protein product.
- Generation and analysis of let-756 loss-of-function mutants.
- Germline transformation experiments for rescue assays.
Main Results:
- A C. elegans gene encoding a 425 amino acid protein with FGF core homology was identified and shown to be transcribed.
- let-756 is expressed throughout post-embryonic development, peaking in larval stages.
- Partial loss-of-function alleles resulted in slow development and smaller size, while a null allele caused early larval arrest.
- The let-756 null phenotype was rescued by the wild-type fgf gene.
Conclusions:
- The C. elegans let-756 gene encodes a functional FGF.
- let-756 is essential for normal larval development and growth in C. elegans.
- This study establishes let-756 as a key developmental gene in nematodes, unlike the previously studied egl-17 fgf gene.