Murine fibroblast growth factor receptor 1 alpha isoforms mediate node regression and are essential for posterior mesoderm development

Alternative spicing in the fibroblast growth factor receptor 1 (Fgfr1) locu s generates a variety of splicing isoforms, including FGFR1 alpha isoforms, which contain three immunoglobulin-like loops in the extracellular domain of the receptor. It has been previously shown that embryos carrying targete d disruptions of all major isoforms die during gastrulation, displaying sev ere growth retardation and defective mesodermal structures. Here we selecti vely disrupted the FGER1 alpha isoforms and found that they play an essenti al role in posterior mesoderm formation during gastrulation. We show that t he mutant embryos lack caudal somites, develop spina bifida, and die at 9.5 -12.5 days of embryonic development because they are unable to establish em bryonic circulation. The primary defect is a failure of axial mesoderm cell migration toward the posterior portions of the embryos during gastrulation , as revealed by regional marker analysis and DiI labeling. In contrast, th e anterior migration of the notochord is unaffected and the embryonic struc tures rostral to the forelimb are relatively normal. These data demonstrate that FGF/FGFR1 alpha signals are posteriorizing factors that control node regression and posterior embryonic development. (C) 1999 Academic Press.