Next-generation sequencing technology provides novel opportunities for gathering genome-scale sequence data in natural populations, laying the empirical foundation for the evolving field of population genomics. Here we conducted a genome scan of nucleotide diversity and differentiation in natural populations of threespine stickleback (Gasterosteus aculeatus). We used Illumina-sequenced RAD tags to identify and type over 45,000 single nucleotide polymorphisms (SNPs) in each of 100 individuals from two oceanic and three freshwater populations. Overall estimates of genetic diversity and differentiation among populations confirm the biogeographic hypothesis that large panmictic oceanic populations have repeatedly given rise to phenotypically divergent freshwater populations. Genomic regions exhibiting signatures of both balancing and divergent selection were remarkably consistent across multiple, independently derived populations, indicating that replicate parallel phenotypic evolution in stickleback may be occurring through extensive, parallel genetic evolution at a genome-wide scale. Some of these genomic regions co-localize with previously identified QTL for stickleback phenotypic variation identified using laboratory mapping crosses. In addition, we have identified several novel regions showing parallel differentiation across independent populations. Annotation of these regions revealed numerous genes that are candidates for stickleback phenotypic evolution and will form the basis of future genetic analyses in this and other organisms. This study represents the first high-density SNP–based genome scan of genetic diversity and differentiation for populations of threespine stickleback in the wild. These data illustrate the complementary nature of laboratory crosses and population genomic scans by confirming the adaptive significance of previously identified genomic regions, elucidating the particular evolutionary and demographic history of such regions in natural populations, and identifying new genomic regions and candidate genes of evolutionary significance.

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Population Genomics of Parallel Adaptation in Threespine Stickleback using Sequenced RAD Tags

Vascular endothelial growth factors (VEGFs) are master regulators of vascular development and of blood and lymphatic vessel function during health and disease in the adult. It is therefore important to understand the mechanism of action of this family of five mammalian ligands, which act through three receptor tyrosine kinases (RTKs). In addition, coreceptors like neuropilins (NRPs) and integrins associate with the ligand/receptor signaling complex and modulate the output. Therapeutics to block several of the VEGF signaling components have been developed with the aim to halt blood vessel formation, angiogenesis, in diseases that involve tissue growth and inflammation, such as cancer. In this review, we outline the current information on VEGF signal transduction in relation to blood and lymphatic vessel biology.

/pdf/signal-transduction-by-vascular-endothelial-growth-factor-2km99omtgf.pdf

Signal Transduction by Vascular Endothelial Growth Factor Receptors

VEGFs (vascular endothelial growth factors) control vascular development during embryogenesis and the function of blood vessels and lymphatic vessels in the adult. There are five related mammalian ligands, which act through three receptor tyrosine kinases. Signalling is modulated through neuropilins, which act as VEGF co-receptors. Heparan sulfate and integrins are also important modulators of VEGF signalling. Therapeutic agents that interfere with VEGF signalling have been developed with the aim of decreasing angiogenesis in diseases that involve tissue growth and inflammation, such as cancer. The present review will outline the current understanding and consequent biology of VEGF receptor signalling.

Signal transduction by vascular endothelial growth factor receptors.

Matrices and scaffolds for delivery of bioactive molecules in bone and cartilage tissue engineering.

Vascular endothelial growth factor (VEGF) represents a growth factor with important pro-angiogenic activity, having a mitogenic and an anti-apoptotic effect on endothelial cells, increasing the vascular permeability, promoting cell migration, etc. Due to these effects, it actively contributes in regulating the normal and pathological angiogenic processes. In humans, the VEGF family is composed of several members: VEGF-A (which has different isoforms), VEGF-B, VEGF-C, VEGF-D, VEGF-E (viral VEGF), VEGF-F (snake venom VEGF), placenta growth factor (PlGF), and, recently, to this family has been added endocrine gland-derived vascular endothelial growth factor (EG-VEGF). VEGF binds to tyrosine kinase cell receptors (VEGFRs): VEGFR-1 [Fms-like tyrosine kinase 1 (Flt-1)], VEGFR-2 [kinase insert domain receptor (KDR) in human; fetal liver kinase 1 (Flk-1) in mouse] and VEGFR-3 [Fms-like tyrosine kinase 4 (Flt-4)]. While VEGFR-1 and VEGFR-2 are expressed predominantly on vascular endothelial cells, VEGFR-3 is expressed especially on lymphatic endothelial cells. VEGFR-2 has the strongest pro-angiogenic activity and a higher tyrosine kinase activity than VEGFR-1. Endothelial cells also express co-receptors, such as neuropilin-1 (NP-1) and neuropilin-2 (NP-2), which modulate tyrosine kinase receptor activity. Both VEGF and VEGFRs are expressed not only on endothelial cells, but also on non-endothelial cells. This article aims to highlight the most recent data referring to the VEGF family and its receptors, as well as its implications in the angiogenesis process. At present, blocking angiogenesis in cancer or in other pathological processes, using anti-VEGF and anti-VEGFRs therapies, is considered to be extremely important.

Vascular endothelial growth factor (VEGF) - key factor in normal and pathological angiogenesis.

Vascular endothelial growth factor-D activates VEGFR-3 expressed in osteoblasts inducing their differentiation

https://febs.onlinelibrary.wiley.com/doi/pdf/10.1016/j.febslet.2008.06.025

Sara Nucciotti

Papers

Vascular endothelial growth factor-D activates VEGFR-3 expressed in osteoblasts inducing their differentiation

Morphogenesis of human endothelial cells is inhibited by DAB2 via Src.