DEAD/H-box proteins are involved in various aspects of RNA metabolism. Here we report the developmental function of a DEAD-box protein, DDX-23, in Caenorhabditis elegans, which has significant homology with the yeast splicing factor PRP28. We found by RNAi and mutant analyses that DDX-23 is essential for both embryonic and post-embryonic development, and required for differentiation of the majority of somatic tissues. When the germline function of ddx-23 was inhibited, hermaphrodite animals showed a reduced number of germ cells and failed to switch from spermatogenesis to oogenesis. These phenotypes were similar to those of the mutants of the three DEAH-box proteins (MOG-1, MOG-4, and MOG-5) whose yeast orthologs are involved in the pre-mRNA splicing pathway. We speculate that DDX-23 functions with the three MOG proteins in the same pathway to regulate tissue differentiation, robust germline proliferation, and the sperm/oocyte switch through modulations of ribonucleoprotein complexes. Developmental Dynamics 237:2367–2377, 2008. © 2008 Wiley-Liss, Inc.