Nucleotide levels regulate germline proliferation through modulating GLP-1/Notch signaling in C. elegans

Area of Science:

• Reproductive Biology
• Molecular Genetics
• Nutrient Metabolism

Background:

• Animals adjust reproduction based on nutrient availability.
• The link between nutrient sensing and reproductive control is not fully understood.
• A mechanism for sensing nucleotide levels to regulate germline proliferation is unknown.

Purpose of the Study:

• To investigate a potential nucleotide-sensing mechanism controlling germline proliferation.
• To explore the role of uridine/thymidine levels in reproductive regulation.
• To identify signaling pathways mediating the effects of nucleotide levels on reproduction.

Main Methods:

• Perturbed nucleotide metabolism in Caenorhabditis elegans and its food source, Escherichia coli.
• Assessed germline proliferation under varying uridine/thymidine (U/T) levels.
• Investigated the roles of GLP-1/Notch, MPK-1/MAPK, IIS, and TORC1 pathways.

Main Results:

• Low U/T levels in food arrested germline proliferation in C. elegans.
• This arrest was critically mediated by GLP-1/Notch and MPK-1/MAPK signaling.
• GLP-1 expression was post-transcriptionally modulated by U/T levels.
• The defect was suppressed by glp-1 hyperactivation but not by IIS or TORC1 pathway activation.

Conclusions:

• A previously unknown nucleotide-sensing mechanism controls reproduction.
• Uridine/thymidine levels directly impact germline proliferation through GLP-1/Notch signaling.
• This finding reveals a novel link between nucleotide metabolism and reproductive control.