The Caenorhabditis elegans presenilin sel-12 is required for mesodermal patterning and muscle function

Area of Science:

• Developmental Biology
• Genetics
• Neuroscience

Background:

• Presenilin gene mutations are linked to familial Alzheimer's disease and affect Notch signaling.
• The Caenorhabditis elegans presenilin SEL-12 plays a role in development.

Purpose of the Study:

• To investigate the function of SEL-12 in Caenorhabditis elegans postembryonic development.
• To understand the molecular mechanisms underlying SEL-12's role in sex muscle development and its connection to egg-laying and mating behaviors.

Main Methods:

• Analysis of sel-12 mutations in Caenorhabditis elegans.
• Genetic rescue experiments using tissue-specific promoters.
• Comparison of sel-12 defects with lin-12 hypomorphic alleles.

Main Results:

• Reduced SEL-12 activity causes late defects in sex muscle development, leading to egg-laying defects in hermaphrodites and reduced mating efficiency in males.
• SEL-12's function in sex muscle development is rescued by expression from the hlh-8 promoter but not late muscle-specific promoters.
• SEL-12 mutations phenocopy lin-12 hypomorphic alleles, suggesting a role in a late LIN-12 signaling event.
• SEL-12 and LIN-12 are involved in distinct signaling pathways affecting sex muscle and pi cell development.

Conclusions:

• SEL-12 is crucial for late postembryonic sex muscle development in Caenorhabditis elegans.
• Impaired SEL-12 function leads to reproductive defects through at least two independent developmental signaling pathways.
• This study highlights a novel role for presenilins in developmental signaling beyond their known roles in neurodegeneration.