Conditional inactivation of VEGF-A in areas of collagen2a1 expression results in embryonic lethality in the heterozygous state

VEGF-A has been implicated in regulating the initial angiogenic invasion ev ents that are essential for endochondral bone formation. VEGF-A mRNA expres sion was indeed found in the sclerotome of the developing somite and in the limb-bud mesenchyme at E10.5 in mouse development but declined during chon drogenesis and became upregulated in hypertrophic chondrocytes prior to ang iogenic invasion. To determine the functional importance of VEGF-A expressi on in the developing chondrogenic tissues, VEGF-A was conditionally inactiv ated during early embryonic development using Collagen2a1-Cre transgenic li nes. Deletion of a single VEGF-A allele in Collagen2a1-Cre-expressing cells results in embryonic lethality around E10.5. This lethality is characteriz ed by aberrant development of the dorsal aorta and intersomitic blood vesse ls, along with defects in the developing endocardial and myocardial layers of the heart. A small percentage of VEGF(Flox/)+, Collagen2a1-Cre fetuses s urvive until E17.5, show aberrant endochondral bone formation and develop a heart phenotype resembling a dilated form of ischemic cardiomyopathy, Thes e results provide insights into the function of VEGF-A in heart and endocho ndral bone formation and underscore the importance of tightly controlled le vels of VEGF-A during development.