Platelet-Derived Growth Factor Receptor β Is Critical for Zebrafish Intersegmental Vessel Formation

نویسندگان

  • Katie M. Wiens
  • Hyuna L. Lee
  • Hiroyuki Shimada
  • Anthony E. Metcalf
  • Michael Y. Chao
  • Ching-Ling Lien
چکیده

BACKGROUND Platelet-derived growth factor receptor beta (PDGFRbeta) is a tyrosine kinase receptor known to affect vascular development. The zebrafish is an excellent model to study specific regulators of vascular development, yet the role of PDGF signaling has not been determined in early zebrafish embryos. Furthermore, vascular mural cells, in which PDGFRbeta functions cell autonomously in other systems, have not been identified in zebrafish embryos younger than 72 hours post fertilization. METHODOLOGY/PRINCIPAL FINDINGS In order to investigate the role of PDGFRbeta in zebrafish vascular development, we cloned the highly conserved zebrafish homolog of PDGFRbeta. We found that pdgfrbeta is expressed in the hypochord, a developmental structure that is immediately dorsal to the dorsal aorta and potentially regulates blood vessel development in the zebrafish. Using a PDGFR tyrosine kinase inhibitor, a morpholino oligonucleotide specific to PDGFRbeta, and a dominant negative PDGFRbeta transgenic line, we found that PDGFRbeta is necessary for angiogenesis of the intersegmental vessels. SIGNIFICANCE/CONCLUSION Our data provide the first evidence that PDGFRbeta signaling is required for zebrafish angiogenesis. We propose a novel mechanism for zebrafish PDGFRbeta signaling that regulates vascular angiogenesis in the absence of mural cells.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Flt-1 (vascular endothelial growth factor receptor-1) is essential for the vascular endothelial growth factor-Notch feedback loop during angiogenesis.

OBJECTIVE Vascular endothelial growth factor (VEGF) signaling induces Notch signaling during angiogenesis. Flt-1/VEGF receptor-1 negatively modulates VEGF signaling. Therefore, we tested the hypothesis that disrupted Flt-1 regulation of VEGF signaling causes Notch pathway defects that contribute to dysmorphogenesis of Flt-1 mutant vessels. APPROACH AND RESULTS Wild-type and flt-1(-/-) mouse e...

متن کامل

DEVELOPMENT AND DISEASE Disruption of acvrl1 increases endothelial cell number in zebrafish cranial vessels

The mechanism by which the embryonic vasculature forms can be divided into two major processes: vasculogenesis and angiogenesis. In vasculogenesis, mesodermally derived endothelial cell precursors or angioblasts migrate to future vessel sites and coalesce with neighbors to form endothelial cell cords, which lumenize and become ensheathed by supporting smooth muscle cells or pericytes. This prim...

متن کامل

Dre-miR-2188 Targets Nrp2a and Mediates Proper Intersegmental Vessel Development in Zebrafish Embryos

BACKGROUND MicroRNAs (miRNAs) are a class of small RNAs that are implicated in the control of eukaryotic gene expression by binding to the 3'UTR of target mRNAs. Several algorithms have been developed for miRNA target prediction however, experimental validation is still essential for the correct identification of miRNA targets. We have recently predicted that Neuropilin2a (Nrp2a), a vascular en...

متن کامل

Intersegmental vessel formation in zebrafish: requirement for VEGF but not BMP signalling revealed by selective and non-selective BMP antagonists.

BACKGROUND AND PURPOSE Bone morphogenetic proteins (BMPs) were first identified through their role in inducing bone and cartilage formation, but many other important functions have since been ascribed to BMPs, including dorsoventral patterning, angiogenesis and tissue homeostasis. Using dorsomorphin and LDN193189, selective small molecule inhibitors of BMP signalling, we investigated the role o...

متن کامل

Hydrogen sulfide improves vessel formation of the ischemic adductor muscle and wound healing in diabetic db/db mice

Objective(s): It has been demonstrated that hydrogen sulfide plays a vital role in physiological and pathological processes such as regulating inflammation, oxidative stress, and vessel relaxation. The aim of the study was to explore the effect of hydrogen sulfide on angiogenesis in the ischemic adductor muscles of type 2 diabetic db/db mice and ischemic diabetic wound...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:

دوره 5  شماره 

صفحات  -

تاریخ انتشار 2010