Targeted disruption of Fgf8 causes failure of cell migration in the gastrulating mouse embryo

Abstract

Fgf8 and Fgf4 encode FGF family members that are coexpressed in the primitive streak of the gastrulating mouse embryo. We have analyzed the phenotype of Fgf8 −/− embryos and discovered that they fail to express Fgf4 in the streak. In the absence of both FGF8 and FGF4, epiblast cells move into the streak and undergo an epithelial-to-mesenchymal transition, but most cells then fail to move away from the streak. As a consequence, no embryonic mesoderm-or endoderm-derived tissues develop, although extraembryonic tissues form. Patterning of the prospective neuroectoderm is greatly perturbed in the mutant embryos. Anterior neuroectoderm markers are widely expressed, at least in part because the anterior visceral endoderm, which provides signals that regulate their expression, is not displaced proximally in the absence of definitive endoderm. Posterior neuroectoderm markers are not expressed, presumably because there is neither mesendoderm underlying the prospective neuroectoderm nor a morphologically normal node to provide the inductive signals necessary for their expression. This study identifies Fgf8 as a gene essential for gastrulation and shows that signaling via FGF8 and/or FGF4 is required for cell migration away from the primitive streak.

Development of the zebrafish inner ear

“…In the zebrafish, this placode cavi- fgf8 (Reifers et al, 1998) Growth factor Small ear, abnormal neurogenesis (Adamska et al, 2000;Phillips et al, 2001) Targeted disruption (Sun et al, 1999) colourless (cls) sox10 (Dutton et al, 2001b) HMG box transcription factor…”

Neptune is involved in posterior axis and tail formation in Xenopus embryogenesis

“…3E). Besides ␣-actin, expression of other mesodermal markers, such as derriere (Sun et al, 1999a), brachyury (Cunliffe and Smith, 1992), and myoD (Hopwood et al, 1989), was elevated in the Neptune-injected caps (data not shown). Thus, it was shown that Neptune has an activity to induce mesoderm directly from animal cap cells even though Neptune is a DNAbinding protein and a factor related to erythropoietic differentiation (Kawahara and Dawid, 2000;Huber et al, 2001).…”

“…Since previous studies showed that FGF-related factors such as brachyury and derriere, have similar posterior-inducing activity (Cunliffe and Smith, 1992;Conlon et al, 1996;Sun et al, 1999a), we further investigated the relationship of these factors. Double staining of neptune and brachyury mRNA in gastrulating embryos indicated that these two transcripts are expressed closely to each other (data not shown).…”

“…In zebrafish, inhibition of the FGF receptor signal leads to complete loss of both the trunk and tail (Griffin et al, 1995). Furthermore, mutant mice lacking FGF8 are unable to undergo normal gastrulation, leading to loss of mesoderm-and endoderm-derived tissues (Sun et al, 1999a). These findings suggest that the FGF signal A well-studied factor that is located downstream of FGF signaling is brachyury.…”

Fibroblast growth factor 8 is expressed at higher levels in lactating human breast and in breast cancer

“…FGF8 was originally isolated from the conditioned medium of an androgen dependent mouse mammary carcinoma line (SC-3) as an androgen induced growth factor (AIGF) and was later assigned as a member of the fibroblast growth factor family on the basis of structural similarity (Tanaka et al, 1992). FGF8 appears to have an important role in embryogenesis and is expressed in several areas of the developing mouse and may play a critical role in gastrulation and the development of the face, limb and central nervous system (Vogel et al, 1996;Neubuser et al, 1997;Meyers et al, 1998;Ye et al, 1998;Tucker et al, 1999;Sun et al, 1999). Little expression of FGF8 has been found in adult mouse tissues with comparatively low amounts detected only in the ovaries and testes (MacArthur et al, 1995a;Lorenzi et al, 1995).…”