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

Autor: Min-Hsuan Lin, Li-En Jao, Yung-Jen Chuang, Lawrence Yu Min Liu, Jie Peng Jiang, Zih Yin Lai, Yi Ching Huang
Rok vydání: 2016
Předmět:
0301 basic medicine
Nervous system
Angiogenesis
Endocrinology
Diabetes and Metabolism
Clinical Biochemistry
Medical and Health Sciences
0302 clinical medicine
Receptors
Pharmacology (medical)
Zebrafish
Tube formation
Motor Neurons
Receptors
Notch
Neurogenesis
Intracellular Signaling Peptides and Proteins
General Medicine
Anatomy
Biological Sciences
Cell biology
medicine.anatomical_structure
Neurological
cardiovascular system
Neurovascular interactions
Signal Transduction
Biochemistry & Molecular Biology
Notch
1.1 Normal biological development and functioning
Neovascularization
Physiologic
Biology
03 medical and health sciences
Underpinning research
Information and Computing Sciences
medicine
Animals
Thrombospondins
Physiologic
Molecular Biology
Neovascularization
Biochemistry
medical
Thrombospondin
Research
Thsd7a
Biochemistry (medical)
Neurosciences
Membrane Proteins
Cell Biology
Motor neuron
Zebrafish Proteins
biology.organism_classification
030104 developmental biology
030217 neurology & neurosurgery
Zdroj: Journal of biomedical science, vol 23, iss 1
Journal of Biomedical Science
Popis: 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. Electronic supplementary material The online version of this article (doi:10.1186/s12929-016-0277-9) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE
Externí odkaz: