Dual roles of the C-terminal Src kinase (Csk) during developmental vascularization

Li-Juan Duan1, Akira Imamoto, Guo-Hua Fong

  • 1Center for Vascular Biology, University of Connecticut Health Center, 263 Farmington Ave, Farmington, CT 06030-3501, USA.

Blood
|October 25, 2003
PubMed

Insights

C-terminal Src kinase (Csk) is crucial for blood vessel development, particularly for forming new blood vessels and remodeling existing ones. Its absence leads to severe vascular defects and embryonic lethality.

Area of Science:

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

Background:

  • C-terminal Src kinase (Csk) is a tyrosine kinase that negatively regulates Src family kinases.
  • Src family kinases play roles in various cellular processes, including cell growth, differentiation, and survival.
  • Vascular development, including angiogenesis and vascular remodeling, is a complex process regulated by numerous signaling pathways.

Purpose of the Study:

  • To investigate the role of Csk in vascular development.
  • To determine the specific processes of vascular development that are affected by Csk deficiency.
  • To explore the potential mechanisms by which Csk influences vascular development.

Main Methods:

  • Generation and analysis of Csk-deficient (Csk(-/-)) mouse embryos.
  • Creation of chimeric embryos composed of wild-type and Csk(-/-) cells.
  • Histological examination of embryonic vasculature.

Main Results:

  • Csk(-/-) embryos exhibited defects in angiogenic sprouting and vascular remodeling, despite initial formation of capillary-like networks.
  • In chimeric embryos, wild-type cells partially rescued the ability of Csk(-/-) endothelial cells to participate in branching morphogenesis.
  • Csk(-/-) embryos displayed failure in vitelline vessel formation and died at embryonic day 9.5.

Conclusions:

  • Csk is essential for normal vascular development, specifically for angiogenic sprouting and vascular remodeling.
  • Wild-type cells may provide factors that support Csk(-/-) endothelial cell function in vascular development.
  • Csk plays a critical role in ensuring embryonic survival through its function in vascular development.

Related Concept Videos

M-Cdk Drives Transition Into Mitosis02:15

M-Cdk Drives Transition Into Mitosis

Checkpoints throughout the cell cycle serve as safeguards and gatekeepers, allowing the cell cycle to progress in favorable conditions and slow or halt it in problematic ones. This regulation is known as the cell cycle control system.
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
Cytoskeletal Coordination in Cell Migration01:32

Cytoskeletal Coordination in Cell Migration

A migrating cell changes its shape during the cyclic events of attachment and detachment from the substratum and repositions the cell organelles correspondingly. These complex events are orchestrated by the dynamic cytoskeletal network comprising actin filaments, intermediate filaments, and microtubules. Cytoskeletal crosstalk — the direct and indirect communication between the different components — is crucial for this coordination. Direct communication involves various linker proteins that...
Mechanism of Angiogenesis01:10

Mechanism of Angiogenesis

Blood vessel formation starts early during embryonic development, around day 7. In the extraembryonic yolk sac, mesodermal precursor cells called hemangioblast proliferate and differentiate into angioblast. Angioblasts express vascular endothelial growth factor receptor 2 or VEGFR2, which binds VEGF-A, a proangiogenic factor, guiding blood vessel formation. VEGF signaling promotes angioblasts to form a blood island in the developing embryo. Angioblasts further differentiate, giving rise to...
Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl hydroxylase and factor...
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...