During development, biomechanical forces contour the body and provide shape to internal organs. We have discovered a regulatory network that is required to maintain epidermal architecture in response to biomechanical forces in C. elegans embryos. Embryos and larvae that are doubly mutant for
mec-8;
sym-3 or
mec-8;
sym-4 have defective anterior morphology, called the Pharynx Ingressed or Pin phenotype. Using a microarray approach, we have discovered that the expression of C. elegans
fbn-1, a fibrillin-related protein, is regulated by a conserved splicing factor, MEC-8/RBPMS, which is required for the correct processing of
fbn-1 mRNA. FBN-1 is secreted at the apical surface of epidermal cells as a component of the embryonic sheath. Acting in a parallel pathway to MEC-8 are two conserved proteins, SYM-3/FAM102B and SYM-4/WDR44, which localize to vesicles at or near the plasma membrane. Our data indicate that SYM-3 and SYM-4 function with the RAB-11 GTPase, a known regulator of endocytic recycling and exocytosis. We have also identified VHA-20/ATP6-
ap2/(P)RR, a multifunctional protein involved in vesicle acidification and planar cell polarity, as enhancing the Pin defect in the
sym-4 mutant background and being critical in RAB-11 recycling endosome localization. Thus, SYM-3-SYM-4-RAB-11 and VHA-20 may promote the correct targeting of FBN-1 or other extracellular matrix proteins to the embryonic sheath. In addition to providing resistance of the epidermis to a pharyngeal pulling force, FBN-1 stabilizes the epidermis during embryonic elongation, when circumferential actomyosin bundles arrayed along the body axis undergo contraction. C. elegans FBN-1 has two integrin-binding RGD domains. We found that mutations in
sym-3 and
sym-4 enhance the notched-head phenotype seen in integrin pathway mutants, suggesting that SYM-3/4 may be important in proper integrin localization. Correspondingly, inhibition of alpha and beta integrins enhances the Pin phenotype in
sym-3,
sym-4, and
fbn-1, indicating that integrins help to maintain structural integrity against biomechanical forces. RNAi studies have revealed that spectrins and cadherins are also a part of this regulatory network to maintain epidermal structure and integrity. Taken together, we have identified a novel network that is required to maintain epidermal architecture in response to a variety of biomechanical forces during embryogenesis.