Bone morphogenetic proteins, eye patterning, and retinocollicular map formation in the mouse.
Patterning events during early eye formation determine retinal cell fate and can dictate the behavior of retinal ganglion cell (RGC) axons as they navigate toward central brain targets. The temporally and spatially regulated expression of bone morphogenetic proteins (BMPs) and their receptors in the retina are thought to play a key role in this process, initiating gene expression cascades that distinguish different regions of the retina, particularly along the dorsoventral axis. Here, we examine the role of BMP and a potential downstream effector, EphB, in retinotopic map formation in the lateral geniculate nucleus (LGN) and superior colliculus (SC). RGC axon behaviors during retinotopic map formation in wild-type mice are compared with those in several strains of mice with engineered defects of BMP and EphB signaling. Normal RGC axon sorting produces axon order in the optic tract that reflects the dorsoventral position of the parent RGCs in the eye. A dramatic consequence of disrupting BMP signaling is a missorting of RGC axons as they exit the optic chiasm. This sorting is not dependent on EphB. When BMP signaling in the developing eye is genetically modified, RGC order in the optic tract and targeting in the LGN and SC are correspondingly disrupted. These experiments show that BMP signaling regulates dorsoventral RGC cell fate, RGC axon behavior in the ascending optic tract, and retinotopic map formation in the LGN and SC through mechanisms that are in part distinct from EphB signaling in the LGN and SC.
Plas
Daniel T
DT
Department of Neuroscience, University of Texas, M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Dhande
Onkar S
OS
Lopez
Joshua E
JE
Murali
Deepa
D
Thaller
Christina
C
Henkemeyer
Mark
M
Furuta
Yasuhide
Y
Overbeek
Paul
P
Crair
Michael C
MC
D000818:Animals; D000831:Animals, Newborn; D055396:Bone Morphogenetic Protein 2; D052005:Bone Morphogenetic Protein Receptors, Type I / Q000235:genetics / Q000378:metabolism; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000502:physiology*; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D005123:Eye / Q000254:growth & development*; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation / Q000502:physiology; D012160:Retina / Q000502:physiology*; D013477:Superior Colliculi / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000502:physiology*; D014795:Visual Pathways / Q000502:physiology; D014981:Xenopus; D000099176:Noggin Protein
D055396:Bone Morphogenetic Protein 2; D052005:Bone Morphogenetic Protein Receptors, Type I; D019485:Bone Morphogenetic Proteins; D002352:Carrier Proteins; D016212:Transforming Growth Factor beta; D000099176:Noggin Protein; C525718:BMP2 protein, human; C525719:Bmp2 protein, mouse