Development of oculomotor axon projections in the chick embryo.
The pattern of innervation of the extraocular muscles is highly conserved across higher vertebrate species and mediates sophisticated visuomotor processes. Defects in oculomotor development often lead to strabismus, a misalignment of the eyes that can cause partial blindness. Although it has been intensively studied from a clinical perspective, relatively little is known about how the system develops embryonically. We have therefore mapped the development of the oculomotor nerve (OMN) in chick embryos by using confocal microscopy. We show that OMN development follows a series of stereotyped steps that are tightly regulated in space and time. The OMN initially grows past three of its targets to innervate its distal target, the ventral oblique muscle, only later forming branches to the more proximal muscles. We have also investigated spatiotemporal aspects of the unusual contralateral migration of a subpopulation of oculomotor neurons by using molecular markers and have found the semaphorin axon guidance molecules and their receptors, the neuropilins, to be expressed in discrete subnuclei during this migration. Finally, we have created an embryological model of Duane retraction syndrome (DRS), a form of strabismus in which the OMN is believed to innervate aberrantly the lateral rectus, the normal target of the abducens nerve. By ablating rhombomeres 5 and 6 and hence the abducens, we have mimicked a proposed oculomotor deficit occurring in DRS. We find that the absence of the abducens nerve is not sufficient to produce this inappropriate innervation, so other factors are required to explain DRS.
Chilton
John Kevin
JK
Medical Research Council Centre for Developmental Neurobiology, Kings College London, Guys Campus, London Bridge, London SE1 1UL, United Kingdom.
Guthrie
Sarah
S
D000010:Abducens Nerve / Q000196:embryology / Q000378:metabolism; D000818:Animals; D001369:Axons / Q000502:physiology*; D002352:Carrier Proteins / Q000378:metabolism; D002642:Chick Embryo; D003598:Cytoskeletal Proteins; D004195:Disease Models, Animal; D004370:Duane Retraction Syndrome / Q000378:metabolism / Q000503:physiopathology; D006023:Glycoproteins / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D060850:LIM-Homeodomain Proteins; D008565:Membrane Proteins; D018613:Microscopy, Confocal / Q000379:methods; D009218:Myosins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D016900:Neurofilament Proteins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism* / Q000502:physiology; D039942:Neuropilin-1 / Q000378:metabolism; D039943:Neuropilin-2 / Q000378:metabolism; D009802:Oculomotor Nerve / Q000166:cytology / Q000196:embryology*; D012333:RNA, Messenger / Q000378:metabolism; D040121:Semaphorin-3A / Q000378:metabolism; D039961:Semaphorins; D014157:Transcription Factors; D014321:Trochlear Nerve / Q000196:embryology / Q000378:metabolism
D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D006023:Glycoproteins; D018398:Homeodomain Proteins; D060850:LIM-Homeodomain Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D016900:Neurofilament Proteins; D039943:Neuropilin-2; D012333:RNA, Messenger; C488217:Sema3a protein, mouse; C111150:Sema3e protein, mouse; D040121:Semaphorin-3A; D039961:Semaphorins; D014157:Transcription Factors; C063843:insulin gene enhancer binding protein Isl-1; D039942:Neuropilin-1; D009218:Myosins