title: Prdm13 regulates subtype specification of retinal amacrine interneurons and modulates visual sensitivity.
abstract: Amacrine interneurons, which are highly diversified in morphological, neurochemical, and physiological features, play crucial roles in visual information processing in the retina. However, the specification mechanisms and functions in vision for each amacrine subtype are not well understood. We found that the Prdm13 transcriptional regulator is specifically expressed in developing and mature amacrine cells in the mouse retina. Most Prdm13-positive amacrine cells are Calbindin- and Calretinin-positive GABAergic or glycinergic neurons. Absence of Prdm13 significantly reduces GABAergic and glycinergic amacrines, resulting in a specific defect of the S2/S3 border neurite bundle in the inner plexiform layer. Forced expression of Prdm13 distinctively induces GABAergic and glycinergic amacrine cells but not cholinergic amacrine cells, whereas Ptf1a, an upstream transcriptional regulator of Prdm13, induces all of these subtypes. Moreover, Prdm13-deficient mice showed abnormally elevated spatial, temporal, and contrast sensitivities in vision. Together, these results show that Prdm13 regulates development of a subset of amacrine cells, which newly defines an amacrine subtype to negatively modulate visual sensitivities. Our current study provides new insights into mechanisms of the diversification of amacrine cells and their function in vision.
authors.affiliation: Laboratory for Molecular and Developmental Biology, Institute for Protein Research, Osaka University, JST, Core Research for Evolutional Science and Technology, 3-2 Yamadaoka, Suita, Osaka, 565-0871, Japan, and Kyoto University Graduate School of Medicine, Yoshida-konoe, Sakyo-ku, 606-8501, Kyoto, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Watanabe
authors.affiliation: Laboratory for Molecular and Developmental Biology, Institute for Protein Research, Osaka University, JST, Core Research for Evolutional Science and Technology, 3-2 Yamadaoka, Suita, Osaka, 565-0871, Japan, and.
authors.forename: Rikako
authors.initials: R
authors.lastname: Sanuki
authors.affiliation: Laboratory for Molecular and Developmental Biology, Institute for Protein Research, Osaka University, JST, Core Research for Evolutional Science and Technology, 3-2 Yamadaoka, Suita, Osaka, 565-0871, Japan, and.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Sugita
authors.affiliation: Laboratory for Molecular and Developmental Biology, Institute for Protein Research, Osaka University.
authors.forename: Wataru
authors.initials: W
authors.lastname: Imai
authors.affiliation: Laboratory for Molecular and Developmental Biology, Institute for Protein Research, Osaka University, JST, Core Research for Evolutional Science and Technology, 3-2 Yamadaoka, Suita, Osaka, 565-0871, Japan, and.
authors.forename: Ryoji
authors.initials: R
authors.lastname: Yamazaki
authors.affiliation: Laboratory for Molecular and Developmental Biology, Institute for Protein Research, Osaka University.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kozuka
authors.affiliation: Laboratory for Molecular and Developmental Biology, Institute for Protein Research, Osaka University.
authors.forename: Mizuki
authors.initials: M
authors.lastname: Ohsuga
authors.affiliation: Laboratory for Molecular and Developmental Biology, Institute for Protein Research, Osaka University, JST, Core Research for Evolutional Science and Technology, 3-2 Yamadaoka, Suita, Osaka, 565-0871, Japan, and takahisa.furukawa@protein.osaka-u.ac.jp.
authors.forename: Takahisa
authors.identifier: http://orcid.org/0000-0003-4171-220X
authors.initials: T
authors.lastname: Furukawa
mesh_terms: D025042:Amacrine Cells / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D059329:Cholinergic Neurons / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D015350:Contrast Sensitivity; D059330:GABAergic Neurons / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics / Q000378:metabolism*; D007395:Interneurons / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D055495:Neurogenesis; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D014157:Transcription Factors; C000599910:Prdm13 protein, mouse; D011495:Histone-Lysine N-Methyltransferase
keywords: Prdm13; amacrine cell; interneuron; retina; subtype specification; visual function