title: Excess HB-EGF, which promotes VEGF signaling, leads to hydrocephalus.
abstract: Heparin binding epidermal growth factor-like growth factor (HB-EGF) is an angiogenic factor mediating radial migration of the developing forebrain, while vascular endothelial growth factor (VEGF) is known to influence rostral migratory stream in rodents. Cell migratory defects have been identified in animal models of hydrocephalus; however, the relationship between HB-EGF and hydrocephalus is unclear. We show that mice overexpressing human HB-EGF with β-galactosidase reporter exhibit an elevated VEGF, localization of β-galactosidase outside the subventricular zone (SVZ), subarachnoid hemorrhage, and ventriculomegaly. In Wistar polycystic kidney rats with hydrocephalus, alteration of migratory trajectory is detected. Furthermore, VEGF infusions into the rats result in ventriculomegaly with an increase of SVZ neuroblast in rostral migratory stream, whereas VEGF ligand inhibition prevents it. Our results support the idea that excess HB-EGF leads to a significant elevation of VEGF and ventricular dilatation. These data suggest a potential pathophysiological mechanism that elevated HB-EGF can elicit VEGF induction and hydrocephalus.
authors.affiliation: Department of Neurosurgery, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA.|Department of Biology, Indiana University Purdue University, Indianapolis, IN 46202, USA.|Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA.
authors.forename: Joon W
authors.initials: JW
authors.lastname: Shim
authors.affiliation: Vascular Biology Program, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA.|Department of Pathology, Stanford University School of Medicine, 300 Pasteur Drive L235, Stanford, CA 94305, USA.|Clinical Microbiology Laboratory, Stanford University Medical Center, 3375 Hillview Avenue Palo, Alto, CA 94304, USA.
authors.forename: Johanna
authors.initials: J
authors.lastname: Sandlund
authors.affiliation: Department of Neurosurgery, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA.|Department of Neurology, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Mustafa Q
authors.initials: MQ
authors.lastname: Hameed
authors.affiliation: Department of Biology, Indiana University Purdue University, Indianapolis, IN 46202, USA.
authors.forename: Bonnie
authors.initials: B
authors.lastname: Blazer-Yost
authors.affiliation: Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
authors.forename: Feng C
authors.initials: FC
authors.lastname: Zhou
authors.affiliation: Vascular Biology Program, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA.|Department of Surgery and Pathology, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Klagsbrun
authors.affiliation: Department of Neurosurgery, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Madsen
mesh_terms: D000818:Animals; D002465:Cell Movement; D002552:Cerebral Ventricles / Q000473:pathology*; D042783:Endothelial Cells / Q000378:metabolism; D066257:Heparin-binding EGF-like Growth Factor / Q000378:metabolism*; D006801:Humans; D006849:Hydrocephalus / Q000378:metabolism* / Q000473:pathology; D020547:Lateral Ventricles / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D015398:Signal Transduction; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: C587883:HBEGF protein, human; D066257:Heparin-binding EGF-like Growth Factor; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse