The Musashi proteins MSI1 and MSI2 are required for photoreceptor morphogenesis and vision in mice

Autor: Fatimah Matalkah, Jesse Sundar, Visvanathan Ramamurthy, Bohye Jeong, Peter Stoilov
Rok vydání: 2020
Předmět:
0301 basic medicine
TTC8
tetratricopeptide repeat domain 8
Msi1
retina
genetic structures
Cellular differentiation
RNA-binding protein
ONL
outer nuclear layer
PNA
peanut agglutinin
Biochemistry
Synaptic Transmission
Msi2
Musashi
Mice
MAK
male germ cell–associated kinase
RBDs
RNA-binding domains
MSI1
Musashi-1
Mice
Knockout
P
postnatal day
Retinal Degeneration
RNA-Binding Proteins
INL
inner nuclear layer
PBST
PBS supplemented with 0.1% Triton X-100
Photoreceptor outer segment
Cell biology
medicine.anatomical_structure
Photoreceptor Cells
Vertebrate
Research Article
Morphogenesis
Nerve Tissue Proteins
Biology
MSI2
Musashi-2
PDE6β
phosphodiesterase-6β
CC
connecting cilium
03 medical and health sciences
splicing
Ciliogenesis
medicine
Animals
Cilia
Peripherin 2
Outer nuclear layer
ERG
electroretinographic
Molecular Biology
Vision
Ocular
Retina
030102 biochemistry & molecular biology
Alternative splicing
Cell Biology
photoreceptor
eye diseases
Alternative Splicing
030104 developmental biology
sense organs
PRPH2
peripherin-2
Zdroj: The Journal of Biological Chemistry
ISSN: 1083-351X
Popis: The Musashi family of RNA-binding proteins is known for its role in stem-cell renewal and is a negative regulator of cell differentiation. Interestingly, in the retina, the Musashi proteins MSI1 and MSI2 are differentially expressed throughout the cycle of retinal development, with MSI2 protein displaying robust expression in the adult retinal tissue. In this study, we investigated the importance of Musashi proteins in the development and function of photoreceptor neurons in the retina. We generated a pan-retinal and rod photoreceptor neuron-specific conditional KO mouse lacking MSI1 and MSI2. Independent of the sex, photoreceptor neurons with simultaneous deletion of Msi1 and Msi2 were unable to respond to light and displayed severely disrupted photoreceptor outer segment morphology and ciliary defects. Mice lacking MSI1 and MSI2 in the retina exhibited neuronal degeneration, with complete loss of photoreceptors within 6 months. In concordance with our earlier studies that proposed a role for Musashi proteins in regulating alternative splicing, the loss of MSI1 and MSI2 prevented the use of photoreceptor-specific exons in transcripts critical for outer segment morphogenesis, ciliogenesis, and synaptic transmission. Overall, we demonstrate a critical role for Musashi proteins in the morphogenesis of terminally differentiated photoreceptor neurons. This role is in stark contrast with the canonical function of these two proteins in the maintenance and renewal of stem cells.
Databáze: OpenAIRE
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