Regulation of pontine neurite morphology by target-derived signals.
The molecular cues that regulate neurite morphology within the target environment are key to the formation of complex neural circuitry. During development of the ponto-cerebellar projection, pontine fibers sprout and form elaborate arbors within the inner cerebellar layer prior to arrival of their target cells, the cerebellar granule neurons. Here, we describe the biochemical fractionation of two granule neuron-derived factors that stimulate elaboration of pontine neurites. These factors were identified using a dissociated pontine bioassay and biochemically fractionated from granule cell (GC) conditioned medium (GCCM). One of the factors, STIM1, is a protein with a molecular weight greater than 30 kDa that is distinct from known neurotrophins. The other, STIM2, is a small, protease-resistant molecule with an estimated molecular weight below 1 kDa. We show that these factors stimulate pontine neurite elongation both independently and cooperatively and thus may contribute to the formation of elaborate pontine arbors within the cerebellar cortex.
Hansen
Stig K
SK
Department of Molecular and Cell Biology, University of California at Berkeley, 265 LSA, Berkeley, CA 94720, USA. hansen@sunesis.com
Szpara
Moriah L
ML
Serafini
Tito A
TA
D000818:Animals; D000831:Animals, Newborn; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D003463:Cues; D017077:Culture Media, Conditioned / Q000737:chemistry / Q000494:pharmacology; D020439:Growth Cones / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D008970:Molecular Weight; D009414:Nerve Growth Factors / Q000302:isolation & purification / Q000378:metabolism* / Q000494:pharmacology; D009434:Neural Pathways / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D016501:Neurites / Q000187:drug effects / Q000378:metabolism*; D011149:Pons / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
D017077:Culture Media, Conditioned; D009414:Nerve Growth Factors