Discrete roles for secreted and transmembrane semaphorins in neuronal growth cone guidance in vivo.
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.
Isbister
C M
CM
Program in Neuroscience, Department of Anatomy, University of British Columbia, Vancouver, BC, V6T 1Z3, Canada.
Tsai
A
A
Wong
S T
ST
Kolodkin
A L
AL
O'Connor
T P
TP
D000595:Amino Acid Sequence; D000818:Animals; D001369:Axons / Q000502:physiology / Q000648:ultrastructure; D019521:Body Patterning; D004625:Embryo, Nonmammalian / Q000502:physiology*; D004848:Epithelium / Q000196:embryology; D018507:Gene Expression Regulation, Developmental; D017344:Genes, Insect; D006110:Grasshoppers / Q000196:embryology*; D018878:Limb Buds / Q000502:physiology; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D008969:Molecular Sequence Data; D009024:Morphogenesis; D009414:Nerve Growth Factors / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D009420:Nervous System / Q000196:embryology*; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D039961:Semaphorins; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
D008565:Membrane Proteins; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; C103150:Sema4d protein, mouse; D039961:Semaphorins