title: Motor neuron-derived Thsd7a is essential for zebrafish vascular development via the Notch-dll4 signaling pathway.
abstract: BACKGROUND
  Development of neural and vascular systems displays astonishing similarities among vertebrates. This parallelism is under a precise control of complex guidance signals and neurovascular interactions. Previously, our group identified a highly conserved neural protein called thrombospondin type I domain containing 7A (THSD7A). Soluble THSD7A promoted and guided endothelial cell migration, tube formation and sprouting. In addition, we showed that thsd7a could be detected in the nervous system and was required for intersegmental vessels (ISV) patterning during zebrafish development. However, the exact origin of THSD7A and its effect on neurovascular interaction remains unclear.
  
  
  RESULTS
  In this study, we discovered that zebrafish thsd7a was expressed in the primary motor neurons. Knockdown of Thsd7a disrupted normal primary motor neuron formation and ISV sprouting in the Tg(kdr:EGFP/mnx1:TagRFP) double transgenic zebrafish. Interestingly, we found that Thsd7a morphants displayed distinct phenotypes that are very similar to the loss of Notch-delta like 4 (dll4) signaling. Transcript profiling further revealed that expression levels of notch1b and its downstream targets, vegfr2/3 and nrarpb, were down-regulated in the Thsd7a morphants. These data supported that zebrafish Thsd7a could regulate angiogenic sprouting via Notch-dll4 signaling during development.
  
  
  CONCLUSIONS
  Our results suggested that motor neuron-derived Thsd7a plays a significant role in neurovascular interactions. Thsd7a could regulate ISV angiogenesis via Notch-dll4 signaling. Thus, Thsd7a is a potent angioneurin involved in the development of both neural and vascular systems.
authors.affiliation: Department of Medical Science & Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu, 30013, Taiwan.|Division of Cardiology, Department of Internal Medicine, Mackay Memorial Hospital Hsinchu Branch, Hsinchu, 30071, Taiwan.
authors.forename: Lawrence Yu-Min
authors.initials: LY
authors.lastname: Liu
authors.affiliation: Department of Medical Science & Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu, 30013, Taiwan.
authors.forename: Min-Hsuan
authors.initials: MH
authors.lastname: Lin
authors.affiliation: Department of Medical Science & Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu, 30013, Taiwan.
authors.forename: Zih-Yin
authors.initials: ZY
authors.lastname: Lai
authors.affiliation: Department of Medical Science & Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu, 30013, Taiwan.
authors.forename: Jie-Peng
authors.initials: JP
authors.lastname: Jiang
authors.affiliation: Department of Medical Science & Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu, 30013, Taiwan.
authors.forename: Yi-Ching
authors.initials: YC
authors.lastname: Huang
authors.affiliation: Department of Cell Biology and Human Anatomy, UC Davis School of Medicine, 4415 Tupper Hall, One Shields Avenue, Davis, CA, 95616, USA.
authors.forename: Li-En
authors.initials: LE
authors.lastname: Jao
authors.affiliation: Department of Medical Science & Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu, 30013, Taiwan. yjchuang@life.nthu.edu.tw.
authors.forename: Yung-Jen
authors.initials: YJ
authors.lastname: Chuang
mesh_terms: D000818:Animals; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009046:Motor Neurons / Q000378:metabolism*; D018919:Neovascularization, Physiologic / Q000502:physiology*; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D019699:Thrombospondins / Q000235:genetics / Q000378:metabolism*; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D051880:Receptors, Notch; D019699:Thrombospondins; D029961:Zebrafish Proteins; C064045:delta protein; C561474:thrombospondin type I domain containing 7A, zebrafish
keywords: Angiogenesis; Neurogenesis; Neurovascular interactions; Notch; Thsd7a