title: Transmembrane semaphorin signalling controls  laminar stratification in the mammalian retina.
abstract: In the vertebrate retina, establishment of precise synaptic connections among distinct retinal neuron cell types is critical for processing visual information and for accurate visual perception. Retinal ganglion cells (RGCs), amacrine cells and bipolar cells establish stereotypic neurite arborization patterns to form functional neural circuits in the inner plexiform layer (IPL), a laminar region that is conventionally divided into five major parallel sublaminae. However, the molecular mechanisms governing distinct retinal subtype targeting to specific sublaminae within the IPL remain to be elucidated. Here we show that the transmembrane semaphorin Sema6A signals through its receptor PlexinA4 (PlexA4) to control lamina-specific neuronal stratification in the mouse retina. Expression analyses demonstrate that Sema6A and PlexA4 proteins are expressed in a complementary fashion in the developing retina: Sema6A in most ON sublaminae and PlexA4 in OFF sublaminae of the IPL. Mice with null mutations in PlexA4 or Sema6A exhibit severe defects in stereotypic lamina-specific neurite arborization of tyrosine hydroxylase (TH)-expressing dopaminergic amacrine cells, intrinsically photosensitive RGCs (ipRGCs) and calbindin-positive cells in the IPL. Sema6A and PlexA4 genetically interact in vivo for the regulation of dopaminergic amacrine cell laminar targeting. Therefore, neuronal targeting to subdivisions of the IPL in the mammalian retina is directed by repulsive transmembrane guidance cues present on neuronal processes.
authors.affiliation: The Solomon H. Snyder Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
authors.forename: Ryota L
authors.initials: RL
authors.lastname: Matsuoka
authors.forename: Kim T
authors.initials: KT
authors.lastname: Nguyen-Ba-Charvet
authors.forename: Aijaz
authors.initials: A
authors.lastname: Parray
authors.forename: Tudor C
authors.initials: TC
authors.lastname: Badea
authors.forename: Alain
authors.initials: A
authors.lastname: Chédotal
authors.forename: Alex L
authors.initials: AL
authors.lastname: Kolodkin
mesh_terms: D025042:Amacrine Cells / Q000201:enzymology / Q000378:metabolism; D000818:Animals; D064026:Calbindins; D002462:Cell Membrane / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism; D020869:Gene Expression Profiling; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009419:Nerve Tissue Proteins; D016501:Neurites / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D012160:Retina / Q000166:cytology* / Q000196:embryology / Q000378:metabolism*; D012165:Retinal Ganglion Cells / Q000378:metabolism; D017299:Rod Opsins / Q000378:metabolism; D064030:S100 Calcium Binding Protein G / Q000378:metabolism; D039961:Semaphorins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D000099210:Melanopsin
chemical_list: D064026:Calbindins; D004298:Dopamine; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D011956:Receptors, Cell Surface; D017299:Rod Opsins; D064030:S100 Calcium Binding Protein G; D039961:Semaphorins; D014446:Tyrosine 3-Monooxygenase; D000099210:Melanopsin; C492110:Plxna4 protein, mouse; C504203:Sema6a protein, mouse