Formation of mesoderm tissue requires an intact FGF signalling pathway downstream of Brachyury. This requirement is due to a regulatory loop, in which Brachyury activates expression of a member of the FGF family, and FGF maintains expression of Brachyury.(ABSTRACT TRUNCATED AT 250 WORDS)

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We have identified a shared homozygous mutation in three families in T and linked it to a novel syndrome consisting of sacral agenesis, a persistent notochordal canal and abnormal ossification of the vertebral bodies. We suggest that screening for the ossification of the vertebrae is warranted in patients with sacral agenesis to evaluate the possible causal involvement of T.

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To cite this article: Tournoij E, Weber GJ, Akkerman JWN, de Groot PG, Zon LI, Moll FL, Schulte-Merker S. Mlck1a is expressed in zebrafish thrombocytes and is an essential component for thrombus formation. J Thromb Haemost 2010; 8: 588-95. Summary. Background:We have used the advantages of the zebrafish model system to demonstrate which of the vertebrate Myosin Light Chain Kinase (MLCK) genes is expressed in thrombocytes and important for thrombus formation. Methods and Results: Here we report that Mlck1a is an essential component of thrombus formation. Phylogenetic data revealed four zebrafish orthologous for three human MLCK genes. To investigateexpressionofthezebrafish mlckgenesinthrombocytes wecomparedGFP-taggedplateletswithother cellsbymicroarray analysis, and showed that mlck1a expression was 4.5-fold enriched in platelets. Furthermore, mlck1a mRNA and mRNA for the platelet-specific cd41 co-localized in thrombi. Expression of other mlck subtypes was lower in GFP-tagged platelets (mlck1b; 0.77-fold enriched) and absent in thrombi (mlck1b, -2, -3). To investigate the role of Mlck1a in thrombus formation, we knocked down mlck1a using two morpholinos. This resulted in impaired morphology changes of platelets adhering on fibrinogen. In a thrombosis model, in which thrombocytes adhere to the vessel wall damaged by laser irradiation, thrombus formation was slowed down in mlck1a-deficient embryos. Conclusion: We conclude that Mlck1a is the subtype of MLCK that contributes to platelet shape change and thrombus formation.

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