Dataset Information

Essential Roles of Tbr1 in the Formation and Maintenance of the Orientation-Selective J-RGCs and a Group of OFF-Sustained RGCs in Mouse.

ABSTRACT: In the mouse retina, more than 30 retinal ganglion cell (RGC) subtypes have been classified based on a combined metric of morphological and functional characteristics. RGCs arise from a common pool of retinal progenitor cells during embryonic stages and differentiate into mature subtypes in adult retinas. However, the cellular and molecular mechanisms controlling formation and maturation of such remarkable cellular diversity remain unknown. Here, we demonstrate that T-box transcription factor T-brain 1 (Tbr1) is expressed in two groups of morphologically and functionally distinct RGCs: the orientation-selective J-RGCs and a group of OFF-sustained RGCs with symmetrical dendritic arbors. When Tbr1 is genetically ablated during retinal development, these two RGC groups cannot develop. Ectopically expressing Tbr1 in M4 ipRGCs during development alters dendritic branching and density but not the inner plexiform layer stratification level. Our data indicate that Tbr1 plays critical roles in regulating the formation and dendritic morphogenesis of specific RGC types.

SUBMITTER: Kiyama T

PROVIDER: S-EPMC6542366 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Publications

Essential Roles of Tbr1 in the Formation and Maintenance of the Orientation-Selective J-RGCs and a Group of OFF-Sustained RGCs in Mouse.

Kiyama Takae T Long Ye Y Chen Ching-Kang CK Whitaker Christopher M CM Shay Allison A Wu Hongyu H Badea Tudor C TC Mohsenin Amir A Parker-Thornburg Jan J Klein William H WH Mills Stephen L SL Massey Stephen C SC Mao Chai-An CA

Cell reports 20190401 3

In the mouse retina, more than 30 retinal ganglion cell (RGC) subtypes have been classified based on a combined metric of morphological and functional characteristics. RGCs arise from a common pool of retinal progenitor cells during embryonic stages and differentiate into mature subtypes in adult retinas. However, the cellular and molecular mechanisms controlling formation and maturation of such remarkable cellular diversity remain unknown. Here, we demonstrate that T-box transcription factor T- ...[more]

PMID: 30995485

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Project description:Outer membrane protein (OMP) biogenesis in Escherichia coli is a robust process essential to the life of the organism. It is catalyzed by the ?-barrel assembly machine (Bam) complex, and a number of quality control factors, including periplasmic chaperones and proteases, maintain the integrity of this trafficking pathway. Little is known, however, about how periplasmic proteases recognize and degrade OMP substrates when assembly is compromised or whether different proteases recognize the same substrate at distinct points in the assembly pathway. In this work, we use well-defined assembly-defective mutants of LptD, the essential lipopolysaccharide assembly translocon, to show that the periplasmic protease DegP degrades substrates with assembly defects that prevent or impair initial contact with Bam, causing the mutant protein to accumulate in the periplasm. In contrast, another periplasmic protease, BepA, degrades a LptD mutant substrate that has engaged the Bam complex and formed a nearly complete barrel. Furthermore, we describe the role of the outer membrane lipoprotein YcaL, a protease of heretofore unknown function, in the degradation of a LptD substrate that has engaged the Bam complex but is stalled at an earlier step in the assembly process that is not accessible to BepA. Our results demonstrate that multiple periplasmic proteases monitor OMPs at distinct points in the assembly process.IMPORTANCE OMP assembly is catalyzed by the essential Bam complex and occurs in a cellular environment devoid of energy sources. Assembly intermediates that misfold can compromise this essential molecular machine. Here we demonstrate distinctive roles for three different periplasmic proteases that can clear OMP substrates with folding defects that compromise assembly at three different stages. These quality control factors help ensure the integrity of the permeability barrier that contributes to the intrinsic resistance of Gram-negative organisms to many antibiotics.

Dataset Information

Essential Roles of Tbr1 in the Formation and Maintenance of the Orientation-Selective J-RGCs and a Group of OFF-Sustained RGCs in Mouse.

Publications

Essential Roles of Tbr1 in the Formation and Maintenance of the Orientation-Selective J-RGCs and a Group of OFF-Sustained RGCs in Mouse.

Similar Datasets

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