Auto-attraction of neural precursors and their neuronal progeny impairs neuronal migration.
Limited neuronal migration into host brain tissue is a key challenge in neural transplantation. We found that one important mechanism underlying this phenomenon is an intrinsic chemotactic interaction between the grafted neural precursor cells (NPCs) and their neuronal progeny. NPCs secrete the receptor tyrosine kinase ligands FGF2 and VEGF, which act as chemoattractants for neurons. Interference with these signaling pathways resulted in enhanced migration of human neurons from neural clusters.
1] Institute of Reconstructive Neurobiology, LIFE and BRAIN Center, University of Bonn and Hertie Foundation, Bonn, Germany. [2].
Julia
J
Ladewig
1] Institute of Reconstructive Neurobiology, LIFE and BRAIN Center, University of Bonn and Hertie Foundation, Bonn, Germany. [2].
Philipp
P
Koch
Institute of Reconstructive Neurobiology, LIFE and BRAIN Center, University of Bonn and Hertie Foundation, Bonn, Germany.
Oliver
O
Brüstle
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D002454:Cell Differentiation; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D015194:Diffusion Chambers, Culture; D000089622:Doublecortin Domain Proteins; D053595:Embryonic Stem Cells / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000276:immunology / Q000494:pharmacology; D005434:Flow Cytometry; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D064231:Nestin / Q000378:metabolism; D058953:Neural Stem Cells / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism; D009924:Organ Culture Techniques; D042461:Vascular Endothelial Growth Factor A / Q000276:immunology / Q000494:pharmacology
D000906:Antibodies; D000089622:Doublecortin Domain Proteins; D004791:Enzyme Inhibitors; D008869:Microtubule-Associated Proteins; D064231:Nestin; D009479:Neuropeptides; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D049452:Green Fluorescent Proteins