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Review
. 2014 Aug;100(8):608-22.
doi: 10.1002/bdra.23283. Epub 2014 Aug 13.

Traffic jam in the primitive streak: the role of defective mesoderm migration in birth defects

Nils J Herion  1 , J Michael Salbaum, Claudia Kappen
Affiliations
Review

Traffic jam in the primitive streak: the role of defective mesoderm migration in birth defects

Nils J Herion et al. Birth Defects Res A Clin Mol Teratol. 2014 Aug.

Abstract

Gastrulation is the process in which the three germ layers are formed that contribute to the formation of all major tissues in the developing embryo. We here review mouse genetic models in which defective gastrulation leads to mesoderm insufficiencies in the embryo. Depending on severity of the abnormalities, the outcomes range from incompatible with embryonic survival to structural birth defects, such as heart defects, spina bifida, or caudal dysgenesis. The combined evidence from the mutant models supports the notion that these congenital anomalies can originate from perturbations of mesoderm specification, epithelial-mesenchymal transition, and mesodermal cell migration. Knowledge about the molecular pathways involved may help to improve strategies for the prevention of major structural birth defects.

Keywords: Fgf signaling; VACTERL; Wnt signaling; basement membrane; caudal regression; cell accumulation; cell adhesion; cell migration; endoderm; epithelial-mesenchymal transition; gastrulation; maternal diabetes; mouse mutant; neural tube defect; neuroepithelium; spinal cord.

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Figures

FIGURE 1.
FIGURE 1.
Generation of mesoderm in the primitive streak through epithelial-mesenchymal transition and cell migration. Epiblast cells are organized in a columnar epithelium (blue). With onset of expression of T/Brachyury (red) and as cells approach the primitive streak, epiblast cells undergo epithelial–mesenchymal transition (EMT) and ingress through the primitive streak (white arrows), ultimately migrating away anteriorly (not pictured) and laterally (black arrows) into the mesodermal wings between the epithelium and the endoderm (green). Abnormalities in the process are evidenced by cell accumulation in the primitive streak, morphologically obvious as a protrusion into the amniotic cavity (brown line). Mutations involved in this phenotype (question mark) and the outcomes from cell accumulation at the primitive streak are the focus of this review.
See this image and copyright information in PMC

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