The C. elegans pharynx undergoes elongation and morphogenesis to its characteristic bi-lobed shape between the 2- and 3-fold stages of embryogenesis. During this period, the pharyngeal muscles and marginal cells forming the isthmus between the anterior and posterior pharyngeal bulbs elongate and narrow. We have identified the spontaneous mutant
pyr-1(
cu8) exhibiting defective pharyngeal isthmus elongation, cytoskeletal organization defects, and maternal effect lethality.
pyr-1 encodes CAD, a trifunctional enzyme required for de novo pyrimidine synthesis, and
pyr-1(
cu8) mutants are rescued by supplying exogenous pyrimidines. Similar pharyngeal defects and maternal effect lethality were found in
sqv-1,
sqv-8,
rib-1 and
rib-2 mutants, which affect enzymes involved in heparan sulfate proteoglycan (HSPG) synthesis.
rib-1 mutant lethality was enhanced in a
pyr-1 mutant background, indicating that HSPG synthesis is very sensitive to decreased pyrimidine pools, and HS disaccharides are moderately decreased in both
rib-1 and
pyr-1 mutants. We hypothesize that HSPGs are necessary for pharyngeal isthmus elongation, and
pyr-1 functions upstream of proteoglycan synthesizing enzymes by providing precursors of UDP-sugars essential for HSPG synthesis.