VEGFR1: a developmental link between neuronal migration and vasculogenesis

Monday, September 22, 2014 — Poster Session I
12:00 p.m. – 2:00 p.m.	FAES Academic Center	NINDS	DEVBIO-3

* FARE Award Winner

Authors

• EM Flannery
• D Donohue
• S Wray

Abstract

Neuronal migration is essential during development for appropriate circuitry to form. Disruption of neuronal migration causes various neurological disease states. In vertebrates, appropriate migration of gonadotropin-releasing hormone-1 (GnRH) neurons to their final location within the brain is necessary for hypothalamic control of sexual maturation and reproductive function. Failure of this process leads to hypogonadotropic hypogonadism (HH), resulting in delayed puberty and infertility. To discover ligand/receptor signaling impacting this migration, we compared the transcriptomes of migratory vs. post-migratory GnRH neurons. The receptor tyrosine kinase Fms-like tyrosine kinase 1 (or vascular endothelial growth factor receptor-1, VEGFR1) was upregulated in migrating neurons. Single cell PCR and immunocytochemistry confirmed expression of VEGFR1 in migrating GnRH neurons. Notably, two VEGFR1 ligands, VEGFA and VEGFB, were expressed along the GnRH migratory route and in GnRH cells, respectively, lending credence to their potential role in regulating GnRH neuronal migration. Functional assays revealed treatment with a VEGFR1-specific blocking antibody decreased GnRH migration distance and rate. These data demonstrate a novel role for VEGFR1 and its ligands in neuronal migration and may provide new candidates for genetic screening in HH patients. Furthermore, this work provides an under-explored link between two critical developmental processes—vasculogenesis and neuronal migration.

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