Neurotrophins and extracellular matrix molecules modulate sensory axon outgrowth.
Neurotrophins have been known to play a pivotal role in axonal guidance. Recent research has implicated the role of extracelluar matrix molecules in co-ordinating axonal movement. In this study, we examined the influence of neurotrophins (nerve growth factor (NGF) and neurotrophin-3 (NT-3)) and extracellular matrix molecules (laminin, fibronectin, and poly-l-lysin) on sensory neurite outgrowth in thoracic dorsal root ganglia (DRG) dissected from rats at embryonic day 13. Adjacent DRG were embedded in a collagen gel matrix and supplemented with NGF or NT-3. Under NT-3 conditions, DRG axons extended towards each other and intermingled, while neurites from NGF-treated DRG demonstrated a strong repellent effect, resulting in turning responses and growth cone collapse. This effect was not observed on a collagen culture surface. Interestingly, the composition of the extracellular matrix strongly influenced the observed repellent effect. Sensory neurites from NGF-stimulated DRG again demonstrated a repellent effect when plated on a laminin surface, but showed intermingling behavior when plated on poly-l-lysin or fibronectin. This observation suggests that a factor secreted by NGF-treated DRG axons interacts with laminin, enabling repulsion. This factor and its interaction with the extracellular matrix play an important role in the mechanism of sensory axonal pathfinding.
Hari
Ashwinii
A
Department of Molecular Neurobiology, Neuroscience Research Center, Humboldt University Hospital Charité, Central Campus, Hufelandweg 14, 10117 Berlin, Germany.
Djohar
Baharak
B
Skutella
Thomas
T
Montazeri
Sonia
S
D000818:Animals; D019521:Body Patterning / Q000502:physiology; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D003463:Cues; D005109:Extracellular Matrix / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000378:metabolism* / Q000494:pharmacology; D005333:Fetus; D005353:Fibronectins / Q000378:metabolism / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D020439:Growth Cones / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D007797:Laminin / Q000378:metabolism / Q000494:pharmacology; D020932:Nerve Growth Factor / Q000378:metabolism / Q000494:pharmacology; D009414:Nerve Growth Factors / Q000378:metabolism* / Q000494:pharmacology; D009475:Neurons, Afferent / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D020933:Neurotrophin 3 / Q000378:metabolism / Q000494:pharmacology; D011107:Polylysine / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D012867:Skin / Q000294:innervation
D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D007797:Laminin; D009414:Nerve Growth Factors; D020933:Neurotrophin 3; D011107:Polylysine; D020932:Nerve Growth Factor