Harald Schnürch

High affinity VEGF binding and developmental expression suggest Flk-1 as a major regulator of vasculogenesis and angiogenesis

Examination of flk-1 receptor tyrosine kinase mRNA expression by in situ hybridization analysis revealed specific association with endothelial cells at all stages of mouse development, including the blood islands in the yolk sac of day 8.5-10.5 embryos, in which the early progenitors of this lineage originate. flk-1 transcripts were abundant in proliferating endothelial cells of vascular sprouts and branching vessels of embryonic and early postnatal brain, but were drastically reduced in adult brain, where proliferation has ceased. Identification of the angiogenic mitogen, vascular endothelial growth factor (VEGF), as the high affinity ligand of Flk-1 and correlation of the temporal and spatial expression pattern of Flk-1 and VEGF suggest a major role of this ligand-receptor signaling system in vasculogenesis and angiogenesis.

A Novel 7-Transmembrane Receptor Expressed in Nerve Growth Factor-Dependent Sensory Neurons ☆

This study reports on the full-length cDNA cloning of a gene identified on the basis of its preferential expression in nerve growth factor, compared with neurotrophin-3-dependent neurons. It encodes a putative 7-transmembrane polypeptide that is distantly related to other members of the G protein-coupled receptor superfamily. Unique features of this receptor include a very long carboxy-terminal tail of 360 amino acids and a specific expression pattern in the chick peripheral nervous system, including nerve growth factor-dependent sensory and sympathetic neurons, as well as enteric neurons. In the central nervous system, the receptor is strongly developmentally regulated and is expressed at high levels in the external granule cell layer of the cerebellum, as well as in motoneurons of the spinal cord, and in retinal ganglion cells.

Regulation of Embryonic Blood Vessel Formation

Endothelial cell turnover within normal adult tissues generally appears to be very low and is in the range of months or even years (Denekamp, 1984). In contrast, the proliferation rate of endothelial cells lining the blood vessels that are involved in tumor vascularization is very high and in the range of a few days (Engermann et al., 1967). The massive formation of new blood vessels is not an exclusive characteristic of tumor development, but also occurs in other pathological conditions like diabetic retinopathies or rheumatoid arthritis. It can also be observed during wound healing as well as during ovulation and corpus luteum formation in the female adult, but in these instances the angiogenic process seems to be regulated by control mechanisms that prevent an overshooting reaction. This controlled angiogenic process may be termed physiological angiogenesis to distinguish it from the aberrant formation of blood vessels under various pathological conditions.