E2F4 Is Required for Early Eye Patterning

Ruzhynsky, Vladimir; Furimsky, Marosh; Park, David; Wallace, Valerie A.; Slack, Ruth S.

doi:10.1159/000210186

Cited by 7 publications

(4 citation statements)

References 96 publications

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“…Rb‐associated E2F4 transcription factor is another negative regulator of Shh signaling. It prevents the lateral displacement of Shh expression from the ventral midline, which otherwise promotes the expansion of optic stalk markers into the optic cup domain during early eye development (Ruzhynsky et al, ). It is also of note that, after the waning of Shh expression from the prechordal plate, the hypothalamus serves as a secondary Shh signaling center under Sox2 and Sox3 regulation to induce optic disc formation (Zhao et al, ).…”

Section: Patterning and Morphogenesis Of The Optic Stalkmentioning

confidence: 99%

Development of astrocytes in the vertebrate eye

Tao

Zhang

2014

Developmental Dynamics

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Astrocytes represent the earliest glial population in the embryonic optic nerve, contributing critically to retinal angiogenesis and formation of brain-retinal-barrier (BRB). Despite of many developmental and clinical implications of astrocytes, answers to some of the most fundamental questions of this unique type of glial cells remain elusive. This review provides an overview of the current knowledge about the origination, proliferation and differentiation of astrocytes, their journey from the optic nerve towards the neuroretina, and their involvement in physiological and pathological development of the visual system.

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Section: Patterning and Morphogenesis Of The Optic Stalkmentioning

confidence: 99%

Development of astrocytes in the vertebrate eye

Tao

Zhang

2014

Developmental Dynamics

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“…Moreover, E2F4 participates in the differentiation of multiple cell types, including the differentiation of myocytes [ 22 , 36 , 67 , 68 , 69 ], neural cells [ 30 , 70 ], adipocytes [ 71 , 72 , 73 , 74 ], hematopoietic cells [ 75 ], chondrocytes [ 76 ], extra-embryonic tissues [ 77 ], endothelial cells [ 78 ], epithelial cells [ 79 ], and multiciliated cells [ 80 , 81 ]. E2F4 can also regulate eye and brain patterning [ 82 , 83 , 84 , 85 ], as well as endocytosis and water channel transport in the testes [ 81 ].…”

Section: E2f4 As a Multifactorial Regulatormentioning

confidence: 99%

E2F4DN Transgenic Mice: A Tool for the Evaluation of E2F4 as a Therapeutic Target in Neuropathology and Brain Aging

Ramón-Landreau

Sánchez‐Puelles

López-Sánchez

et al. 2022

IJMS

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E2F4 was initially described as a transcription factor with a key function in the regulation of cell quiescence. Nevertheless, a number of recent studies have established that E2F4 can also play a relevant role in cell and tissue homeostasis, as well as tissue regeneration. For these non-canonical functions, E2F4 can also act in the cytoplasm, where it is able to interact with many homeostatic and synaptic regulators. Since E2F4 is expressed in the nervous system, it may fulfill a crucial role in brain function and homeostasis, being a promising multifactorial target for neurodegenerative diseases and brain aging. The regulation of E2F4 is complex, as it can be chemically modified through acetylation, from which we present evidence in the brain, as well as methylation, and phosphorylation. The phosphorylation of E2F4 within a conserved threonine motif induces cell cycle re-entry in neurons, while a dominant negative form of E2F4 (E2F4DN), in which the conserved threonines have been substituted by alanines, has been shown to act as a multifactorial therapeutic agent for Alzheimer’s disease (AD). We generated transgenic mice neuronally expressing E2F4DN. We have recently shown using this mouse strain that expression of E2F4DN in 5xFAD mice, a known murine model of AD, improved cognitive function, reduced neuronal tetraploidization, and induced a transcriptional program consistent with modulation of amyloid-β (Aβ) peptide proteostasis and brain homeostasis recovery. 5xFAD/E2F4DN mice also showed reduced microgliosis and astrogliosis in both the cerebral cortex and hippocampus at 3-6 months of age. Here, we analyzed the immune response in 1 year-old 5xFAD/E2F4DN mice, concluding that reduced microgliosis and astrogliosis is maintained at this late stage. In addition, the expression of E2F4DN also reduced age-associated microgliosis in wild-type mice, thus stressing its role as a brain homeostatic agent. We conclude that E2F4DN transgenic mice represent a promising tool for the evaluation of E2F4 as a therapeutic target in neuropathology and brain aging.

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“…Moreover, E2F4 participate in the differentiation of multiple cell types, including the diferentiation of myocytes [22,36,[67][68][69], neural cells [30,70], adipocytes [71][72][73][74], hematopoietic cells [75], chondrocytes [76], extra-embryonic tissues [77], endothelial cells [78], epithelial cells [79], and multiciliated cells [80,81]. E2F4 can also regulate eye and brain patterning [82][83][84][85] as well as endocytosis and water channel transport in the testes [81].…”

Section: E2f4 As a Regulator Of Tissue Homeostasismentioning

confidence: 99%

E2F4DN Transgenic Mice: A Tool for the Evaluation of E2F4 as a Therapeutic Target in Neuropathology and Brain Aging

Ramón-Landreau¹,

Sánchez‐Puelles²,

López-Sánchez³

et al. 2022

Preprint

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E2F4 was initially described as a transcription factor with a key function in the regulation of cell quiescence. Nevertheless, a number of recent studies have established that E2F4 can also play a relevant role in cell and tissue homeostasis as well as tissue regeneration. For these non-canonical functions, E2F4 can also act in the cytoplasm, where it is able to interact with many homeostatic and synaptic regulators. Since E2F4 is expressed in the nervous system, it may fulfill a crucial role in brain function and homeostasis, being a promising multifactorial target for neurodegenerative diseases and brain aging. The regulation of E2F4 is complex as it can be chemically modified through acetylation, from which we present evidence in the brain, as well as methylation, and phosphorylation. The phosphorylation of E2F4 within a conserved threonine motif induces cell cycle re-entry in neurons, while a dominant negative form of E2F4 (E2F4DN), in which the conserved threonines have been substituted by alanines, has been shown to act as a multifactorial therapeutic agent for Alzheimer’s disease (AD). We have generated transgenic mice neuronally expressing E2F4DN. We have recently shown using this mouse strain that expression of E2F4DN in 5xFAD mice, a known murine model of AD, improved cognitive function, reduced neuronal tetraploidization, and induced a transcriptional program consistent with modulation of amyloid-beta (Abeta) peptide proteostasis and brain homeostasis recovery. 5xFAD/E2F4DN mice also showed reduced microgliosis and astrogliosis in both cerebral cortex and hippocampus at 3-6 months of age. Here we have analyzed the immune response in 1 year-old 5xFAD/E2F4DN mice, concluding that reduced microgliosis and astrogliosis is maintained at this late stage. In addition, the expression of E2F4DN also reduced age-associated microgliosis in wild-type mice, thus stressing its role as a brain homeostatic agent. We conclude that E2F4DN transgenic mice represent a promising tool for the evaluation of E2F4 as a therapeutic target in neuropathology and brain aging.

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E2F4 Is Required for Early Eye Patterning

Cited by 7 publications

References 96 publications

Development of astrocytes in the vertebrate eye

Development of astrocytes in the vertebrate eye

E2F4DN Transgenic Mice: A Tool for the Evaluation of E2F4 as a Therapeutic Target in Neuropathology and Brain Aging

E2F4DN Transgenic Mice: A Tool for the Evaluation of E2F4 as a Therapeutic Target in Neuropathology and Brain Aging

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