Answers to Questions in Text
Somitomeres into Somites (p. 346/347)
Dorsal Aorta Formation in Xenopus (p. 359/360)
Clarifications and Corrections
p.360, left column, line 2 should read: immediately ventral to the hypochord. Shortly...
New Review Articles
Cleaver O. and Krieg P. (2001) Notochord patterning of the endoderm. Devel. Biol. 234: 1-12
Grapin-Botton A. and Melton D.A. (2000) Endoderm development from patterning to organogenesis. trends in genet. 16: 124-130
Ornitz D.M. and Marie P.J. (2002) FGF signaling pathways in endochondral and intramembranous bone development and human genetic disease. genes & Devel. 16: 1446-1465
Stainier D.Y.R. (2002) A glimpse into the molecular entrails of endoderm formation. Genes & Devel. 16: 893-907
New Research Articles
Mariani F.W., Choi G.B. and Harland R.M. (2001) The neural plate specifies somite size in the Xenopus laevis gastrula. Devel. Cell 1: 115-126
Xenopus embryos injected unilaterally with mRNA for the transcriptional inhibitor XBF-2 develop with an expanded neural plate on the injected side. Remarkably, the ectopic neural tissue is complemented by extra somitic mesoderm, as indicated by MyoD+ expression. Overexpression of other signals that neuralize the ectoderm, such as Smad-6 or Ŗ-catenin cause similar somite enlargements. The somite expansion is associated with a reduced expression of molecular markers for intermediate and lateral plate mesoderm. Conversely, replacement of prospective neural plate with tissue refractory to neural induction is followed by reduced somite formation. Thus, the dorsoventral patterning of the mesoderm involves not only Spemann's organizer but also signals from neuroectoderm.
Dubrulle J., McGrew M.J. and Pourquiť O. (2001) FGF signaling controls somite boundary position and regulates segmentation clock control of spatiotempopral Hox gene activation. Cell 106: 219-232
ZŠkŠny J., Kmita M., Alarcon P., de la Pompa J.-L. abd Duboule D. (2001) Localized and transient transcription of Hox genes suggests a link between patterning and the segmentation clock. Cell 106: 207-217
Both studies support a long-standing model known as "clock and wavefront". According to this model, an autonomous timer, the segmentation clock, interacts with a wavefront that converts clock phases into spatial cues. The model has received support earlier from the discovery of several genes whose expression in presomitic mesoderm (PSM) oscillates with the same periodicity as somite formation. If the clock were linked to a counting mechanism it could also provide a link between the placement of segment boundaries and the establishment of different segment identities.
Dubrulle et al. provide evidence that the wavefront may be a sharp gradient of fibroblast growth factor-8 (FGF-8) within the PSM. In chicken embryos, the FGF-8 gradient normally moves posteriorly as Hensen's node and the PSM recede. As predicted by the model, forced and wide-spread expression of FGF keeps the PSM in an undifferentiated state. Applying FGF-8 locally in a bead causes the formation of smaller-than-normal somites in front of the bead and larger-than-normal somites behind the bead. Once the somites are formed they express the appropriate combination of Hox genes, which determine the segment-specific morphology. The observations of Dubrulle et al. on embryos with manipulated numbers and sizes of somites indicate that the embryo counts somites rather than measuring their absolute anteroposterior position.
ZŠkŠny et al. find that several Hox genes are activated during somite formation in the PSM. The activation pattern of Hoxd1 and Hoxd3 coincides with a wave of expression of lunatic fringe+, a gene that is controlled by Notch signaling, which is considerd to be part of the segmentation clock. Mice deficient in RBPJk, a signal protein downstream of Notch, fail to activate Hoxd1 and Hoxd3 properly. Once a Hox gene is activated by the clock, its anterior boundary of expression is maintained at the level of the somite that was formed when the gene was switched on. Thus, these studies provide a link between segmentation and Hox gene activation. However, it remains to be established how each Hox gene is activated at the appropriate clock cycle, and why the sequence of gene activation follows the colinearity rule.
Holley SA, JŁlich D, Rauch GJ, Geisler R, NŁsslein-Volhard C. (2002) her1 and the notch pathway function within the oscillator mechanism that regulates zebrafish somitogenesis. Development 129: 1175-1183
In both mouse and zebrafish, the notch pathway is is involved in stripes/waves of gene expression that precede somite formation. This study on zebrafish was done to clarify whether the notch pathway is part of the oscillator mechanism itself or if the notch pathway simply coordinates the activity of the oscillator among neighboring cells. Oscillations in the expression of the hairy-related transcription factor her1, and the notch ligand deltaC, were monitored in the mutants aei/deltaD and des/notch1, in 'morpholino knockdowns' of deltaC and her1, and in double 'mutant' combinations. This analysis indicates that these oscillations in gene expression are created by a genetic circuit comprised of the notch pathway and the notch target gene her1.
Great SEMs and drawings of mouse and human embryonic development may be found on this web site, which is slated for additional illustrations of pre-implantation and fetal development as well as the genesis of birth defects.
The Multidimensional Human Embryo is funded by the National Institute of Child Health and Human Development (NICHD) and provides a three-dimensional image reference of the Human Embryo based on magnetic resonance imaging.
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