Sequential activation of p75 and TrkB is involved in dendritic development of subventricular zone-derived neuronal progenitors in vitro.
Dendritic arbor development of subventricular zone-derived interneurons is a critical step in their integration into functional circuits of the postnatal olfactory bulb. However, the mechanism and molecular control of this process remain unknown. In this study, we have developed a culture model where dendritic development of purified subventricular zone cells proceeds under serum-free conditions in the absence of added growth factors and non-neural cells. We demonstrate that the large majority of these cells in culture express GABA and elaborate dendritic arbors with spine-like protrusions but they do not possess axons. These neurons expressed receptors for neurotrophins including p75, TrkB and TrkC but not TrkA. Application of exogenous neurotrophins, including brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT3) and nerve growth factor (NGF), to cultures stimulated dendritic growth and led to more complex dendritic arbors during the initial 3 days in culture. Our results suggest that these effects are independent of Trk receptors and mediated by the p75/ceramide signaling pathway. We also show that brain-derived neurotrophic factor is the only neurotrophin that is able to influence late-phase dendritic development via TrkB receptor activation. These results suggest that dendritic arbor development of subventricular zone-derived cells may be regulated by neurotrophins through the activation of p75 and the TrkB receptor signaling pathways in a sequentially defined temporal pattern.
Gascon
E
E
Department of Neuroscience, University of Geneva Medical School, 1 Rue Michel Servet, CH-1211, Geneva, Switzerland.
Vutskits
L
L
Zhang
H
H
Barral-Moran
M J
MJ
Kiss
P J
PJ
Mas
C
C
Kiss
J Z
JZ
D000199:Actins / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology; D016923:Cell Death; D002478:Cells, Cultured; D002552:Cerebral Ventricles / Q000166:cytology*; D018076:DNA, Complementary / Q000096:biosynthesis; D003712:Dendrites / Q000187:drug effects / Q000502:physiology*; D003952:Diagnostic Imaging / Q000379:methods; D019922:GAP-43 Protein / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D020287:In Situ Nick-End Labeling / Q000379:methods; D007381:Intermediate Filament Proteins / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D020932:Nerve Growth Factor / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D064231:Nestin; D039842:Neural Cell Adhesion Molecule L1 / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D020933:Neurotrophin 3 / Q000494:pharmacology; D016133:Polymerase Chain Reaction / Q000379:methods; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020800:Receptor, Nerve Growth Factor; D020917:Receptor, trkA / Q000378:metabolism; D020813:Receptor, trkB / Q000378:metabolism*; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism*; D012794:Sialic Acids / Q000378:metabolism; D013234:Stem Cells / Q000502:physiology*; D013997:Time Factors; D014404:Tubulin / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D000199:Actins; D019208:Brain-Derived Neurotrophic Factor; D018076:DNA, Complementary; D019922:GAP-43 Protein; D007381:Intermediate Filament Proteins; C489787:MAP2 protein, rat; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; C577486:Nes protein, rat; D064231:Nestin; D039842:Neural Cell Adhesion Molecule L1; D020933:Neurotrophin 3; D016760:Proto-Oncogene Proteins c-fos; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor; D012794:Sialic Acids; C488416:Tubb3 protein, rat; D014404:Tubulin; C103469:polysialyl neural cell adhesion molecule; D005680:gamma-Aminobutyric Acid; D020932:Nerve Growth Factor; D020917:Receptor, trkA; D020813:Receptor, trkB