Developmental gene regulatory networks (GRNs) are assemblages of gene regulatory interactions that direct ontogeny of animal body plans. Studies of GRNs operating in early development of euechinoid sea urchins has revealed that little appreciable change has occurred since their divergence approximately 90 million years ago (mya). These observations suggest that strong conservation of GRN architecture has been maintained in early development of the sea urchin lineage. To test whether this is true for all sea urchins, comparative analyses of echinoid taxa that diverged deeper in geological time must be conducted. Recent studies highlighted extensive divergence of skeletogenic mesoderm specification in the sister clade of euechinoids, the cidaroids, suggesting that comparative analyses of cidaroid GRN architecture may confer a greater understanding of the evolutionary dynamics of developmental GRNs. Here, we report spatiotemporal patterning of 55 regulatory genes and perturbation analyses of key regulatory genes involved in euechinoid oral-aboral patterning of non-skeletogenic mesodermal and ectodermal domains in early development of the cidaroid Eucidaris tribuloides. Our results indicate that developmental GRNs directing mesodermal and ectodermal specification have undergone marked alterations since the divergence of cidaroids and euechinoids. Notably, statistical and clustering analyses of echinoid temporal gene expression datasets indicate that regulation of mesodermal genes has diverged more markedly than regulation of ectodermal genes. Although research on indirect-developing euechinoid sea urchins suggests strong conservation of GRN circuitry during early embryogenesis, this study indicates that since the divergence of cidaroids and euechinoids developmental GRNs have undergone significant divergence.