BMP Signaling Functions as a Distinct Pro-Angiogenic Cue

Public Deposited
Analytics

Downloadable Content

Download PDF
Request Version for Screen Reader
Last Modified
  • March 19, 2019
Creator
  • Wiley, David Michael
    • Affiliation: College of Arts and Sciences, Department of Biology
Abstract
  • Angiogenesis, the formation of new blood vessels from pre-existing vessels, is critical for the growth and survival of tissues in both normal and pathological scenarios. Vascular networks observed in vertebrates display a vast array of morphological and functional diversity. Large blood vessels rapidly transport blood to more highly branched capillaries where circulation is slowed and oxygen and nutrients are able to more effectively diffuse into the surrounding tissue. Unfortunately, our understanding of how this morphological diversity is generated is largely unknown. During zebrafish development, we found that angiogenic sprouts from the dorsal aorta are dependent on vascular endothelial growth factor A (VEGFA) signaling, and do not respond to bone morphogenetic protein (BMP) signals. In contrast, the highly branched angiogenic sprouts from the axial vein are regulated by BMP signaling independently of VEGFA signals, indicating that BMP is a vein-specific angiogenic cue during early vascular development. Responding to distinct angiogenic cues, the neighboring dorsal aorta and the axial vein are able to regulate distinct programs of sprouting angiogenesis. When we analyzed the effects of BMP in mammalian systems we found that BMP signaling is a potent and selective regulator of branching morphogenesis. These effects are distinct from VEGFA which has pleiotropic effects on vessel morphogenesis. Upon closer analysis, we find that BMP signaling regulates tip cell morphology during angiogenesis. Interestingly, inhibiting pathways that are known to establish tip cell identity prevents BMP-induced branching in zebrafish. Taken together, our results support a paradigm whereby BMP regulates branching morphogenesis and network diversity via its effects on tip cell responses.
Date of publication
DOI
Resource type
Rights statement
  • In Copyright
Note
  • "... in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Department of Biology."
Advisor
  • Bautch, Victoria
Language
Publisher
Place of publication
  • Chapel Hill, NC
Access right
  • Open access
Date uploaded
  • March 18, 2013

Relations

Parents:

This work has no parents.

Items

Thumbnail Title Date Uploaded Visibility Actions
file details 2019-04-12 Public Download