title: Apoptosis regulates ipRGC spacing necessary for rods and cones to drive circadian photoentrainment.
abstract: The retina consists of ordered arrays of individual types of neurons for processing vision. Here, we show that such order is necessary for intrinsically photosensitive retinal ganglion cells (ipRGCs) to function as irradiance detectors. We found that during development, ipRGCs undergo proximity-dependent Bax-mediated apoptosis. Bax mutant mice exhibit disrupted ipRGC spacing and dendritic stratification with an increase in abnormally localized synapses. ipRGCs are the sole conduit for light input to circadian photoentrainment, and either their melanopsin-based photosensitivity or ability to relay rod/cone input is sufficient for circadian photoentrainment. Remarkably, the disrupted ipRGC spacing does not affect melanopsin-based circadian photoentrainment but severely impairs rod/cone-driven photoentrainment. We demonstrate reduced rod/cone-driven cFos activation and electrophysiological responses in ipRGCs, suggesting that impaired synaptic input to ipRGCs underlies the photoentrainment deficits. Thus, for irradiance detection, developmental apoptosis is necessary for the spacing and connectivity of ipRGCs that underlie their functioning within a neural network.
authors: Department of Biology, Johns Hopkins University, Baltimore, MD 21218, USA.
authors: Shih-Kuo
authors: SK
authors: Chen
authors: Kylie S
authors: KS
authors: Chew
authors: David S
authors: DS
authors: McNeill
authors: Patrick W
authors: PW
authors: Keeley
authors: Jennifer L
authors: JL
authors: Ecker
authors: Buqing Q
authors: BQ
authors: Mao
authors: Johan
authors: J
authors: Pahlberg
authors: Bright
authors: B
authors: Kim
authors: Sammy C S
authors: SC
authors: Lee
authors: Michael A
authors: MA
authors: Fox
authors: William
authors: W
authors: Guido
authors: Kwoon Y
authors: KY
authors: Wong
authors: Alapakkam P
authors: AP
authors: Sampath
authors: Benjamin E
authors: BE
authors: Reese
authors: Rejji
authors: R
authors: Kuruvilla
authors: Samer
authors: S
authors: Hattar
mesh_terms: D000200:Action Potentials / Q000502:physiology / Q000528:radiation effects; D000429:Alcohol Oxidoreductases; D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D051792:Basic Helix-Loop-Helix Proteins / Q000172:deficiency; D055592:Biophysical Phenomena; D002940:Circadian Rhythm / Q000235:genetics / Q000502:physiology*; D056970:Co-Repressor Proteins; D004268:DNA-Binding Proteins / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics / Q000528:radiation effects; D049452:Green Fluorescent Proteins / Q000235:genetics; D020287:In Situ Nick-End Labeling; D066298:In Vitro Techniques; D055537:Light Signal Transduction / Q000502:physiology / Q000528:radiation effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000235:genetics / Q000528:radiation effects; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D010775:Photic Stimulation; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D017949:Retinal Cone Photoreceptor Cells / Q000502:physiology*; D012165:Retinal Ganglion Cells / Q000502:physiology*; D017948:Retinal Rod Photoreceptor Cells / Q000502:physiology*; D017299:Rod Opsins / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D014795:Visual Pathways / Q000502:physiology; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000172:deficiency; D051028:bcl-2-Associated X Protein / Q000172:deficiency; D000099210:Melanopsin
chemical_list: D000429:Alcohol Oxidoreductases; D051792:Basic Helix-Loop-Helix Proteins; D056970:Co-Repressor Proteins; D004268:DNA-Binding Proteins; D049452:Green Fluorescent Proteins; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; D016760:Proto-Oncogene Proteins c-fos; D017299:Rod Opsins; D014446:Tyrosine 3-Monooxygenase; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein; D000099210:Melanopsin; C117638:Atoh7 protein, mouse; C494773:Bak1 protein, mouse; C494827:Bax protein, mouse; C498441:Bsn protein, mouse; C111341:Ctbp2 protein, mouse
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