Motor neuron-derived Thsd7a is essential for zebrafish vascular development via the Notch-dll4 signaling pathway

BackgroundDevelopment 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.ResultsIn 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.ConclusionsOur 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.

• Publication year

  2016

• Venue

  Journal of Biomedical Sciences

• Publication date

  2016-08-02

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1186/s12929-016-0277-9PMID 27484901PMCID 4971630
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• Thsd7a regulates angiogenic sprouting via the Notch-dll4 signaling pathway.

  Confidence 0.90

  All you need is Python (5d7gwfm5zu) extraction뀨 (7c402c1b98) review박진우 (dztg5apj7m) review
• Knockdown of Thsd7a disrupts normal primary motor neuron formation and intersegmental vessel sprouting.

  Confidence 0.95

  All you need is Python (5d7gwfm5zu) extraction뀨 (7c402c1b98) review박진우 (dztg5apj7m) review
• Thsd7a is expressed in the primary motor neurons of zebrafish.

  Confidence 0.95

  All you need is Python (5d7gwfm5zu) extraction뀨 (7c402c1b98) review박진우 (dztg5apj7m) review

• angiogenic sprouting

  biological process

  The biological process by which new blood vessels form from pre-existing ones during zebrafish development.

  All you need is Python (5d7gwfm5zu) extraction뀨 (7c402c1b98) review박진우 (dztg5apj7m) review
• intersegmental vessels

  vascular structure, anatomical structure

  Sprouting blood vessels in zebrafish embryos that require Thsd7a for proper patterning.

  Aliases: ISV

  All you need is Python (5d7gwfm5zu) extraction뀨 (7c402c1b98) review박진우 (dztg5apj7m) review
• notch-dll4 signaling pathway

  signaling pathway

  A cell signaling pathway that regulates vascular development and is modulated by Thsd7a.

  Aliases: Notch-dll4 signaling

  All you need is Python (5d7gwfm5zu) extraction뀨 (7c402c1b98) review박진우 (dztg5apj7m) review
• primary motor neurons

  cell type, neuron

  A specific class of neurons in the zebrafish nervous system identified as the origin of Thsd7a expression.

  All you need is Python (5d7gwfm5zu) extraction뀨 (7c402c1b98) review박진우 (dztg5apj7m) review
• thsd7a

  protein, angioneurin

  A thrombospondin type I domain containing 7A protein identified as an angioneurin involved in neurovascular interactions.

  All you need is Python (5d7gwfm5zu) extraction뀨 (7c402c1b98) review박진우 (dztg5apj7m) review

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