Cdc42 is required in mural cells for proper patterning of the retinal vasculature

• Mural cells constitute the outer lining of blood vessels. They are known as pericytes in the capillary network and referred to as smooth muscle cells (SMC) around arteries and veins. Despite their ubiquity, their contribution to vascular morphogenesis remains obscure. In this work, we investigated the role of Cdc42 in mural cells in vivo, using the developing mouse retina as a model. We find that, during postnatal development, Cdc42 is required in both, pericytes and smooth muscle cells to maintain proper cell morphology, coverage and distribution. During retinal angiogenesis, Cdc42-depleted pericytes lag behind the sprouting front, at least in part due to decreased proliferation. Consequently, capillaries at the sprouting front remain pericyte deprived and are prone to increased vascular leakage. In addition, arteries and arterioles deviate from their normal growth directions and trajectory. While in the adult retina, mural cell coverage normalizes and pericytes adopt a normal morphology, smooth muscle cell morphologies remain abnormal and arteriolar branching angles are markedly reduced. Our findings demonstrate that Cdc42 is required for mural cell proliferation, morphology and distribution and suggest that mural cells are essential for normal vascular morphogenesis of the developing retinal vasculature.

Nyckelord

Cdc42

pericytes

vasculature

retina

mural cells

Biologi med inriktning mot molekylär cellbiologi

Biology with specialization in Molecular Cell Biology

Publikations- och innehållstyp

vet (ämneskategori)

ovr (ämneskategori)