The gene trap method for embryonic stem cells is an efficient method for identifying new genes that are involved in development. Using this method, we identified a novel gene called helicase family gene related to gastrulation (helG). Helicase family proteins regulate many systems in the body that are related to cell survival. HelG encodes a protein of 137 kDa, which contains a DExH helicase motif that is now named DHX30. HelG is strongly expressed in neural cells (ie, in the headfold, neural plate, neural tube, and brain) and somites during embryogenesis. Growing homozygous mutant embryos have neither differentiated somites nor brains. In these mutants, development was retarded by embryonic day 7.5 (E7.5), and the mutants died at E9.5. After the purification of HelG, an untwisting experiment was performed to confirm the helicase activity of HelG for DNA in vitro. We report for the first time that a helicase family gene is required for differentiation during embryogenesis; this gene might interact with polynucleotides to regulate some genes that are important for early development and has a structure similar to that of a human DExH box helicase.