Forced expression of platelet-derived growth factor B in the mouse cerebellar primordium changes cell migration during midline fusion and causes cerebellar ectopia.
The platelet-derived growth factor (PDGF) and receptors are expressed in the developing central nervous system and in brain tumors. To investigate the role of PDGF during normal cerebellar development, we created transgenic mice where PDGF-B was introduced into the endogenous Engrailed1 locus (En1). These mice expressed PDGF-B in all types of cells that constitute the developing cerebellum, with localized high expression in the ventral midline of the cerebellar anlage. This affected cell migration in the midline during fusion of the cerebellar anlage and caused misplacement of midline structures. PDGFR-alpha- and laminin alpha1-positive meningeal cells migrated inwards, attracted by the ectopic transgene expression in the ventral neuroepithelium. Other cells followed the meningeal cells and in the adult mouse, cells from all cortical cell layers were found misplaced in the midline. Moreover, the transgene caused an enhancement of capillary vessels. The findings indicate that normal PDGF signaling is important for proper neural tube fusion. It also illustrates that meningeal structures can influence the process.
Andrae
Johanna
J
Department of Genetics and Pathology, Uppsala University, Rudbeck Laboratory, SE-751 85 Uppsala, Sweden.
Afink
Gijs
G
Zhang
Xiao-Qun
XQ
Wurst
Wolfgang
W
Nistér
Monica
M
D000818:Animals; D019521:Body Patterning / Q000235:genetics; D002196:Capillaries / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D002465:Cell Movement / Q000235:genetics*; D002478:Cells, Cultured; D002531:Cerebellum / Q000002:abnormalities* / Q000166:cytology / Q000378:metabolism; D002828:Choristoma / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D005333:Fetus; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D007763:Lac Operon / Q000235:genetics; D007797:Laminin / Q000378:metabolism; D008578:Meninges / Q000002:abnormalities* / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018919:Neovascularization, Physiologic / Q000235:genetics; D009421:Nervous System Malformations / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D020574:Proto-Oncogene Proteins c-sis / Q000235:genetics / Q000378:metabolism*; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism
D007797:Laminin; D020574:Proto-Oncogene Proteins c-sis; D011993:Recombinant Fusion Proteins; C084098:laminin A; D020796:Receptor, Platelet-Derived Growth Factor alpha