Discrete roles for secreted and transmembrane semaphorins in neuronal growth cone guidance in vivo

Development ◽  
1999 ◽  
Vol 126 (9) ◽  
pp. 2007-2019 ◽  
Author(s):  
C.M. Isbister ◽  
A. Tsai ◽  
S.T. Wong ◽  
A.L. Kolodkin ◽  
T.P. O'Connor
Keyword(s):  
Growth Cone ◽  
Limb Bud ◽  
Axon Outgrowth ◽  
Neuronal Growth ◽  
Neuronal Growth Cone ◽  
Guidance Molecule ◽  
Neuronal Growth Cones ◽  
Guidance Information

From the initial stages of axon outgrowth to the formation of a functioning synapse, neuronal growth cones continuously integrate and respond to multiple guidance cues. To investigate the role of semaphorins in the establishment of appropriate axon trajectories, we have characterized a novel secreted semaphorin in grasshopper, gSema 2a. Sema 2a is expressed in a gradient in the developing limb bud epithelium during Ti pioneer axon outgrowth. We demonstrate that Sema 2a acts as chemorepulsive guidance molecule critical for axon fasciculation and for determining both the initial direction and subsequent pathfinding events of the Ti axon projection. Interestingly, simultaneous perturbation of both secreted Sema 2a and transmembrane Sema I results in a broader range and increased incidence of abnormal Ti pioneer axon phenotypes, indicating that different semaphorin family members can provide functionally distinct guidance information to the same growth cone in vivo.

scholarly journals Modeling the Role of Myosin 1c in Neuronal Growth Cone Turning

2003 ◽  
Vol 85 (5) ◽  
pp. 3319-3328 ◽  
Author(s):  
Feng-Song Wang ◽  
Can-Wen Liu ◽  
Thomas J. Diefenbach ◽  
Daniel G. Jay
Keyword(s):  
Growth Cone ◽  
Neuronal Growth ◽  
Neuronal Growth Cone

scholarly journals Myosin 1c and myosin IIB serve opposing roles in lamellipodial dynamics of the neuronal growth cone

2002 ◽  
Vol 158 (7) ◽  
pp. 1207-1217 ◽  
Author(s):  
Thomas J. Diefenbach ◽  
Vaughan M. Latham ◽  
Dean Yimlamai ◽  
Canwen A. Liu ◽  
Ira M. Herman ◽  
...  
Keyword(s):  
Dorsal Root Ganglion ◽  
Neurite Outgrowth ◽  
Growth Cone ◽  
Dorsal Root ◽  
Myosin Ii ◽  
Growth Cones ◽  
Neuronal Growth ◽  
Rapid Reduction ◽  
Neuronal Growth Cone

The myosin family of motor proteins is implicated in mediating actin-based growth cone motility, but the roles of many myosins remain unclear. We previously implicated myosin 1c (M1c; formerly myosin Iβ) in the retention of lamellipodia (Wang et al., 1996). Here we address the role of myosin II (MII) in chick dorsal root ganglion neuronal growth cone motility and the contribution of M1c and MII to retrograde F-actin flow using chromophore-assisted laser inactivation (CALI). CALI of MII reduced neurite outgrowth and growth cone area by 25%, suggesting a role for MII in lamellipodial expansion. Micro-CALI of MII caused a rapid reduction in local lamellipodial protrusion in growth cones with no effects on filopodial dynamics. This is opposite to micro-CALI of M1c, which caused an increase in lamellipodial protrusion. We used fiduciary beads (Forscher et al., 1992) to observe retrograde F-actin flow during the acute loss of M1c or MII. Micro-CALI of M1c reduced retrograde bead flow by 76%, whereas micro-CALI of MII or the MIIB isoform did not. Thus, M1c and MIIB serve opposite and nonredundant roles in regulating lamellipodial dynamics, and M1c activity is specifically required for retrograde F-actin flow.

scholarly journals Glycogen synthase kinase 3beta phosphorylation of microtubule-associated protein 1B regulates the stability of microtubules in growth cones

1999 ◽  
Vol 112 (19) ◽  
pp. 3373-3384 ◽  
Author(s):  
R.G. Goold ◽  
R. Owen ◽  
P.R. Gordon-Weeks
Keyword(s):  
Growth Cone ◽  
Glycogen Synthase ◽  
Growth Cones ◽  
Microtubule Dynamics ◽  
Neuronal Growth ◽  
Transfected Cells ◽  
Cos Cells ◽  
Glycogen Synthase Kinase 3Beta ◽  
Neuronal Growth Cones

We have recently shown that glycogen synthase kinase 3beta (GSK3beta) phosphorylates the microtubule-associated protein (MAP) 1B in an in vitro kinase assay and in cultured cerebellar granule cells. Mapping studies identified a region of MAP1B high in serine-proline motifs that is phosphorylated by GSK3beta. Here we show that COS cells, transiently transfected with both MAP1B and GSK3beta, express high levels of the phosphorylated isoform of MAP1B (MAP1B-P) generated by GSK3beta. To investigate effects of MAP1B-P on microtubule dynamics, double transfected cells were labelled with antibodies to tyrosinated and detyrosinated tubulin markers for stable and unstable microtubules. This showed that high levels of MAP1B-P expression are associated with the loss of a population of detyrosinated microtubules in these cells. Transfection with MAP1B protected microtubules in COS cells against nocodazole depolymerisation, confirming previous studies. However, this protective effect was greatly reduced in cells containing high levels of MAP1B-P following transfection with both MAP1B and GSK3beta. Since we also found that MAP1B binds to tyrosinated, but not to detyrosinated, microtubules in transfected cells, we propose that MAP1B-P prevents tubulin detyrosination and subsequent conversion of unstable to stable microtubules and that this involves binding of MAP1B-P to unstable microtubules. The highest levels of MAP1B-P are found in neuronal growth cones and therefore our findings suggest that a primary role of MAP1B-P in growing axons may be to maintain growth cone microtubules in a dynamically unstable state, a known requirement of growth cone microtubules during pathfinding. To test this prediction, we reduced the levels of MAP1B-P in neuronal growth cones of dorsal root ganglion cells in culture by inhibiting GSK3beta with lithium. In confirmation of the proposed role of MAP1B-P in maintaining microtubule dynamics we found that lithium treatment dramatically increased the numbers of stable (detyrosinated) microtubules in the growth cones of these neurons.

scholarly journals Monoclonal antibodies show that kinase C phosphorylation of GAP-43 during axonogenesis is both spatially and temporally restricted in vivo.

1991 ◽  
Vol 112 (5) ◽  
pp. 991-1005 ◽  
Author(s):  
K F Meiri ◽  
L E Bickerstaff ◽  
J E Schwob
Keyword(s):  
Growth Cone ◽  
Phosphorylation Site ◽  
Axon Outgrowth ◽  
Kinase C ◽  
Phosphorylated Form ◽  
Cone Function ◽  
Lag Period ◽  
And Function

To study the role of kinase C phosphorylation in the distribution and function of GAP-43 we have generated a panel of mAbs that distinguish between GAP-43 that has been phosphorylated by kinase C and forms that have not. One class of antibodies, typified by 2G12/C7, reacts with only the phosphorylated form of GAP-43; it recognizes the peptide IQAS(PO4)FR equivalent to residues 38-43 that includes the single kinase C phosphorylation site at serine. Another, exemplified by 10E8/E7, reacts with both phosphorylated and nonphosphorylated forms. We have used the antibodies to study the distribution of kinase C-phosphorylated GAP-43 during axonogenesis and in the adult nervous system. Two major findings emerge. First, there is a lag between the initiation of axon outgrowth and the phosphorylation of GAP-43 by kinase C. The extent of this lag period varies between the different structures studied. In some cases, e.g., the trigeminal nerve, our result suggest that kinase C phosphorylation may be correlated with proximity of the growing axon to its target. Second, kinase C-phosphorylated GAP-43 is always spatially restricted to the distal axon. It is never seen either proximally or in cell bodies, even those with high levels of GAP-43 protein. This result also implies that GAP-43 is axonally transported in the non-kinase C phosphorylated form. Thus, kinase C phosphorylation of GAP-43 is not required for axon outgrowth or growth cone function per se and may be more related to interactions of the growth cone with its environment.

scholarly journals Neuronal Growth Cone Retraction Relies on Proneurotrophin Receptor Signaling Through Rac

2011 ◽  
Vol 4 (202) ◽  
pp. ra82-ra82 ◽  
Author(s):  
K. Deinhardt ◽  
T. Kim ◽  
D. S. Spellman ◽  
R. E. Mains ◽  
B. A. Eipper ◽  
...  
Keyword(s):  
Growth Cone ◽  
Receptor Signaling ◽  
Neuronal Growth ◽  
Neuronal Growth Cone

Ultra-short pulses to signal neuronal growth cone machinery

2007 ◽  
Author(s):  
Manoj Mathew ◽  
Ivan Amat-Roldan ◽  
Rosa Andres ◽  
Iain G. Cormack ◽  
David Artigas ◽  
...  
Keyword(s):  
Growth Cone ◽  
Neuronal Growth ◽  
Short Pulses ◽  
Neuronal Growth Cone

The neuronal growth cone as a specialized transduction system

BioEssays ◽  
1991 ◽  
Vol 13 (3) ◽  
pp. 127-134 ◽  
Author(s):  
Stephen M. Strittmatter ◽  
Mark C. Fishman
Keyword(s):  
Growth Cone ◽  
Neuronal Growth ◽  
Neuronal Growth Cone
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