Histamine metabolism influences blood vessel branching in zebrafish <it>reg6 </it>mutants

• Main Authors: Cheng Yih-Shyun E, Huang Chin-Wei, Huang Cheng-chen, Yu John
• Format: Article
• Language: English
• Published: BMC 2008-03-01
• Series: BMC Developmental Biology
• Online Access: http://www.biomedcentral.com/1471-213X/8/31

<p>Abstract</p> <p>Background</p> <p>Vascular branching morphogenesis is responsible for the extension of blood vessels into growing tissues, a process crucial for organogenesis. However, the genetic mechanism for vessel branching is largely unknown. Zebrafish <it>reg6 </it>is a temperature-sensitive mutation exhibiting defects in blood vessel branching which results in the formation of swollen vessel lumina during capillary plexus formation.</p> <p>Results</p> <p>We performed a screening for chemical suppressors of <it>reg6 </it>and identified SKF91488, an inhibitor of histamine methyltransferase (HMT), that can rescue the <it>reg6 </it>vessel branching defects in a dose-dependent manner. Inhibition of HMT by SKF91488 presumably blocks histamine degradation, thus causing histamine accumulation. Consistent with this idea, we found that a high level of histamine also showed significant suppression of <it>reg6 </it>vessel phenotypes. Interestingly, when <it>reg6 </it>adults that had already developed swollen vessel lumina in regenerating fins were treated with histamine or SKF91488, either treatment significantly reduced the number of swollen vessels within 12 h, suggesting a rapid and constant influence of histamine on blood vessel branching. Furthermore, the expression of HMT was significantly elevated in <it>reg6 </it>regenerating fins. Conversely, lowering histamine by administering urocanic acid, a histidine decarboxylase inhibitor, enhanced the <it>reg6 </it>phenotypes. Finally, we identified that the transcription factor, egr-1 (early growth response factor 1), was closely associated with the <it>reg6 </it>phenotype and chemical treatments.</p> <p>Conclusion</p> <p>Taken together, our results suggest that blood vessel branching is influenced by histamine metabolism, possibly through regulating the expression of the egr-1 transcription factor.</p>