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

Lawrence Yu Min Liu, Min Hsuan Lin, Zih Yin Lai, Jie Peng Jiang, Yi Ching Huang, Li-En Jao, Yung Jen Chuang

Research output: Contribution to journalArticle

3 Citations (Scopus)

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.

Original languageEnglish (US)
Article number59
JournalJournal of Biomedical Science
Volume23
Issue number1
DOIs
StatePublished - Aug 2 2016

Fingerprint

Motor Neurons
Zebrafish
Neurons
Blood Vessels
Thrombospondins
Endothelial cells
Neurology
Nervous System
Cell Movement
Vertebrates
Endothelial Cells
Phenotype
Proteins

Keywords

  • Angiogenesis
  • Neurogenesis
  • Neurovascular interactions
  • Notch
  • Thsd7a

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Molecular Biology
  • Cell Biology
  • Biochemistry, medical
  • Endocrinology, Diabetes and Metabolism
  • Pharmacology (medical)

Cite this

Motor neuron-derived Thsd7a is essential for zebrafish vascular development via the Notch-dll4 signaling pathway. / Liu, Lawrence Yu Min; Lin, Min Hsuan; Lai, Zih Yin; Jiang, Jie Peng; Huang, Yi Ching; Jao, Li-En; Chuang, Yung Jen.

In: Journal of Biomedical Science, Vol. 23, No. 1, 59, 02.08.2016.

Research output: Contribution to journalArticle

Liu, Lawrence Yu Min ; Lin, Min Hsuan ; Lai, Zih Yin ; Jiang, Jie Peng ; Huang, Yi Ching ; Jao, Li-En ; Chuang, Yung Jen. / Motor neuron-derived Thsd7a is essential for zebrafish vascular development via the Notch-dll4 signaling pathway. In: Journal of Biomedical Science. 2016 ; Vol. 23, No. 1.
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AB - 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.

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