Resolution of defective dorsal aortae patterning in Sema3E-deficient mice occurs via angiogenic remodeling

Stryder M. Meadows, Lyndsay A. Ratliff, Manvendra K. Singh, Jonathan A. Epstein, Ondine Cleaver

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Background: Neuronal guidance cues influence endothelial cell (EC) behavior to shape the embryonic vascular system. The repulsive neuronal guidance cue, Semaphorin 3E (Sema3E), is critical for creating avascular zones that instruct and subsequently pattern the first embryonic vessels, the paired dorsal aortae (DA). Sema3E-/- embryos develop highly branched plexus-like vessels during vasculogenesis, instead of smooth paired vessels. Unexpectedly, despite these severe DA patterning defects, mutant mice are viable throughout adulthood. Results: Examination of Sema3E-/- mice reveals that the plexus-like DA resolve into single, unbranched vessels between embryonic day (E) E8.25 and E8.75. Although fusion of Sema3E-/- DA occurs slightly earlier than in heterozygotes, the DA are otherwise indistinguishable, suggesting a complete "rescue" in their development. Resolution of the DA null plexuses occurs by remodeling rather than by means of changes in cell proliferation or death. Conclusions: Normalization of Sema3E-/- DA patterning defects demonstrates resilience of embryonic vascular patterning programs. Additional repulsive guidance cues within the lateral plate mesoderm likely re-establish avascular zones lost in Sema3E-/- embryos and guide resolution of mutant plexus into branchless, parallel aortae. Our observations explain how Sema3E-/- mice survive throughout development and into adulthood, despite severe initial vascular defects.

Original languageEnglish (US)
Pages (from-to)580-590
Number of pages11
JournalDevelopmental Dynamics
Volume242
Issue number5
DOIs
StatePublished - May 2013

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Semaphorins
Aorta
Cues
Blood Vessels
Embryonic Structures
Mesoderm
Heterozygote
Cell Death
Endothelial Cells
Cell Proliferation

Keywords

  • Angiogenic remodeling
  • Avascular
  • Endothelial
  • Lateral plate mesoderm
  • Neuronal guidance cue
  • Notochord
  • Repulsive
  • Sema3E

ASJC Scopus subject areas

  • Developmental Biology

Cite this

Resolution of defective dorsal aortae patterning in Sema3E-deficient mice occurs via angiogenic remodeling. / Meadows, Stryder M.; Ratliff, Lyndsay A.; Singh, Manvendra K.; Epstein, Jonathan A.; Cleaver, Ondine.

In: Developmental Dynamics, Vol. 242, No. 5, 05.2013, p. 580-590.

Research output: Contribution to journalArticle

Meadows, Stryder M. ; Ratliff, Lyndsay A. ; Singh, Manvendra K. ; Epstein, Jonathan A. ; Cleaver, Ondine. / Resolution of defective dorsal aortae patterning in Sema3E-deficient mice occurs via angiogenic remodeling. In: Developmental Dynamics. 2013 ; Vol. 242, No. 5. pp. 580-590.
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