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

Vascular endothelial growth factor receptor (VEGFR)-3/Flt4 binds VEGF-C and VEGF-D with high affinity. It has been suggested to be involved in neurogenesis and adult neuronal function. However, little is known about the localization of VEGFR-3 in the adult central nervous system (CNS). The present study presents, to our knowledge, the first detailed mapping of VEGFR-3 mRNA expression in adult rat brain and spinal cord by using in situ hybridization and reverse transcription-polymerase chain reaction analysis (RT-PCR). Varying VEGFR-3 expression intensity was detected in functionally diverse nuclei, with the highest levels in the mitral cells of the olfactory bulb, piriform cortex, anterodorsal thalamic nucleus, several nuclei of the hypothalamus, and the brainstem cranial nerve nuclei. VEGFR-3 mRNA was abundantly expressed in the ventral motor neurons of the spinal cord and in some circumventricular organs such as the median eminence and the area postrema. Moreover, the locus coeruleus and some of the nuclei of the reticular formation showed moderate-to-high hybridization signals. VEGFR-3 expression appeared to be localized mostly within neurons, but weak labeling was also found in some astrocytes. In particular, VEGFR-3 was highly expressed in ependymal cells of the ventral third ventricle and the median eminence, which were co-labeled with vimentin but not with glial fibrillary acidic protein, suggesting that these cells are tanycytes. RT-PCR analysis revealed similar levels of VEGFR-3 expression in all regions of the adult rat CNS. The specific but widespread distribution of VEGFR-3 mRNA in the adult rat CNS suggests that VEGFR-3 functions more broadly than expected, regulating adult neuronal function playing important roles in tanycyte function.