Expression of vascular endothelial growth factor receptor‐3 mRNA in the rat developing forebrain and retina

Abstract

Vascular endothelial growth factor receptor (VEGFR)-3, a receptor for VEGF-C and VEGF-D, is expressed in neural progenitor cells, but there has been no comprehensive study of its distribution in the developing brain. Here, the temporal and cell-specific expression of VEGFR-3 mRNA was studied in the developing rat forebrain and eye. Expression appeared along the ventricular and subventricular zones of the lateral and third ventricles showing ongoing neurogenesis as early as embryonic day 13 but was progressively down-regulated during development and remained in the subventricular zone and rostral migratory stream of the adult forebrain. VEGFR-3 expression was also detectable in some differentiating and postmitotic neurons in the developing cerebral cortex, including Cajal-Retzius cells, cortical plate neurons, and subplate neurons. Expression in the subplate increased significantly during the early postnatal period but was absent by postnatal day 14. It was also highly expressed in nonneural tissues of the eye during development, including the retinal pigment epithelium, the retinal ciliary margin, and the lens, but persisted in a subset of cells in the pigmented ciliary epithelium of the adult eye. In contrast, there was weak or undetectable expression in the early neural retina, but a subset of retinal neurons in the postnatal and mature retina showed intense signals. These unique spatiotemporal mRNA expression patterns suggest that VEGFR-3 might mediate the regulation of both neurogenesis and adult neuronal function in the rat forebrain and eye.

Distribution of vascular endothelial growth factor receptor-3/Flt4 mRNA in adult rat central nervous system

“…Thus, it is possible that VEGFR-3 is expressed in these unique neurogenic zones, which are thought to retain the capacity of generating new neurons and glia in the adult brain. This suggestion is supported by our previous findings (Choi et al, 2010) that VEGFR-3 is expressed in the subventricular zone of the lateral ventricle and the rostral migratory stream of the mature forebrain, where neural stem cells reside (Doetsch et al, 1999;Ihrie and Alvarez-Buylla, 2008;Mendoza-Torreblanca et al, 2008).…”

“…We showed that radial glia in embryonic forebrain, Mü ller glial cells and Bergmann glia expressed VEGFR-3 (Choi et al, 2010;Hou et al, 2011). Furthermore, VEGFR-3 is upregulated in SVZ astrocytes, type B cells in the SVZ of stroke-lesioned rats, which share some characteristics with radial glia-like cells (Shin et al, 2010a).…”

“…We demonstrated that VEGFR-3 might be involved in neuronal precursor cell proliferation and neurogenesis in association with the radial glia in the developing forebrain and cerebellum (Choi et al, 2010;Hou et al, 2011). These studies also showed that the expression of VEGFR-3 mRNA is not confined solely to the fields of cellular proliferation, but it is constitutively expressed in almost all the cortical regions harboring mature neurons and postmitotic neurons in the mature cerebellum, suggesting a possible involvement of VEGFR-3 in adult neuronal function as well as in developmental processes.…”

Evolution of the VEGF-Regulated Vascular Network from a Neural Guidance System

“…The VEGFR3 gene is highly transcribed in postnatal brain both in a subset of retinal neurons and in glial precursor cells [52], whereas VEGF-C and VEGF-D are variably produced by different neuronal and glial cells [22]. In addition, VEGF-C receptor VEGFR3 is expressed in neural progenitor cells in Xenopus laevis and mouse embryos [53].…”

Molecular Parallels between Neural and Vascular Development

“…Vegf-c deletion in the mouse, as well as VEGF-C knockdown in Xenopus tadpoles, inhibited proliferation of neural progenitor cells in the forebrain, without defects of the brain vasculature, indicating that VEGF-C is a trophic factor for subsets of neural progenitor cells in the vertebrate embryonic brain (LeBras et al 2006). The high-affinity VEGF-C receptor VEGFR-3 is also expressed by embryonic and adult neural cells (Choi et al 2010;Calvo et al 2011). Using transgenic VEGFR-3 mice expressing a YFP reporter or conditional deletions of VEGFR-3 in neural cells, we have shown that, in the adult SVZ, VEGF-C/VEGFR-3 signaling acted in niche astrocytes and NSCs to stimulate neurogenesis (Calvo et al 2011).…”