fgf8 mRNA decay establishes a gradient that couples axial elongation to patterning in the vertebrate embryo

Formation and patterning of the vertebrate embryo occur in a head-to-tail sequence. This progressive mode of body formation from the posterior end of the embryo requires a strict temporal coordination of tissue differentiation—a process involving fibroblast growth factor (FGF) signalling. Here we show that transcription of fgf8 messenger RNA is restricted to the growing posterior tip of the embryo. fgf8 mRNA is progressively degraded in the newly formed tissues, resulting in the formation of an mRNA gradient in the posterior part of the embryo. This fgf8 mRNA gradient is translated into a gradient of FGF8 protein, which correlates with graded phosphorylation of the kinase Akt, a downstream effector of FGF signalling. Such a mechanism provides an efficient means to monitor the timing of FGF signalling, coupling the differentiation of embryonic tissues to the posterior elongation of the embryo. In addition, this mechanism provides a novel model for morphogen gradient formation.

[1]  The origin and evolution of segmentation , 1999 .

[2]  J. Collins,et al.  Gene Modulation by the Cyclooxygenase Inhibitor, Sulindac Sulfide, in Human Colorectal Carcinoma Cells , 2003, Journal of Biological Chemistry.

[3]  David Ish-Horowicz,et al.  Expression of a Delta homologue in prospective neurons in the chick , 1995, Nature.

[4]  R. Keynes,et al.  A cell lineage analysis of segmentation in the chick embryo. , 1988, Development.

[5]  R. Hyman,et al.  Kinetics of the in vitro inhibition of transcription by actinomycin. , 1970, Journal of molecular biology.

[6]  K. Storey,et al.  Onset of neuronal differentiation is regulated by paraxial mesoderm and requires attenuation of FGF signalling. , 2002, Development.

[7]  J. Rossant,et al.  Spatial and temporal patterns of ERK signaling during mouse embryogenesis , 2003, Development.

[8]  Scott E Fraser,et al.  Cell Dynamics During Somite Boundary Formation Revealed by Time-Lapse Analysis , 2002, Science.

[9]  G. Martin,et al.  The mouse Fgf8 gene encodes a family of polypeptides and is expressed in regions that direct outgrowth and patterning in the developing embryo. , 1995, Development.

[10]  Claudio D. Stern,et al.  Patterning the Embryonic Axis FGF Signaling and How Vertebrate Embryos Measure Time , 2001, Cell.

[11]  Olivier Pourquié,et al.  FGF Signaling Controls Somite Boundary Position and Regulates Segmentation Clock Control of Spatiotemporal Hox Gene Activation , 2001, Cell.

[12]  A. Kuroiwa,et al.  Fgf/MAPK signalling is a crucial positional cue in somite boundary formation. , 2001, Development.

[13]  N. Bertrand,et al.  FGF signalling controls the timing of Pax6 activation in the neural tube. , 2000, Development.

[14]  C. MacArthur,et al.  Roles for FGF8 in the Induction, Initiation, and Maintenance of Chick Limb Development , 1996, Cell.

[15]  J. Schlessinger.  Cell Signaling by Receptor Tyrosine Kinases , 2000, Cell.

[16]  Scott E. Fraser,et al.  FGF receptor signalling is required to maintain neural progenitors during Hensen's node progression , 2001, Nature Cell Biology.

[17]  W. Yuan,et al.  Mapping Ligand Binding Domains in Chimeric Fibroblast Growth Factor Receptor Molecules , 1999, The Journal of Biological Chemistry.

[18]  M. Catala,et al.  Organization and development of the tail bud analyzed with the quail-chick chimaera system , 1995, Mechanisms of Development.

[19]  Olivier Pourquié,et al.  The lunatic Fringe gene is a target of the molecular clock linked to somite segmentation in avian embryos , 1998, Current Biology.

[20]  J. Gurdon,et al.  Morphogen gradient interpretation , 2001, Nature.