THE EED MUTATION DISRUPTS ANTERIOR MESODERM PRODUCTION IN MICE

Mouse embryos homozygous for the mutation embryonic ectoderm developme nt (eed) exhibit a growth defect and fail to gastrulate normally. Whil e extraembryonic mesoderm is produced extensively, very little embryon ic mesoderm is detected in eed mutant embryos, and there is no subsequ ent organization of mesoderm into node, notochord, or somites. The phe notype is consistent with a defect in the distal primitive streak. Her e we report additional phenotypic analyses that include mRNA in situ h ybridization of genes whose expression reflects the function of differ ent regions of the primitive streak and their derivatives. These studi es have confirmed that mesoderm derived from the proximal primitive st reak is specified appropriately. Despite the absence of a morphologica lly distinct node, sparse axial mesoderm cells in eed mutant embryos a re specified, as reflected by expression of Brachyrury (T), Sonic hedg ehog, and Tcf3b/HNF-3 beta, and definitive endoderm is produced. Speci fication of these cell types is also independent of correct expression of nodal, Fgf4, and gsc. Finally, T and Evx1 display ectopic expressi on in cells not normally fated to ingress through the primitive streak . The data presented are discussed in terms of mechanisms for establis hment of the eed phenotype, and are consistent with the eed gene produ ct playing an early role in primitive streak formation and/or organiza tion.