Characterization of the BAC Id3-enhanced green fluorescent protein transgenic mouse line for<i>in vivo</i>imaging of astrocytes

Lamantia, Cassandra E.; Tremblay, Marie‐Ève; Majewska, Ania K.

doi:10.1117/1.nph.1.1.011014

Cited by 9 publications

(9 citation statements)

References 54 publications

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“…By contrast, Id3 is highly expressed in neural tissues (Figure S3c,h). Double labeling experiments confirmed that all Id3 + cells outside the germinal zone are ALDH1L1+ astrocytes (Figure S3i), as reported by previous studies (Batiuk et al, 2020; Lamantia et al, 2014; Li et al, 2021). Collectively, these data argued against the expression of Id1 and Id3 in oligodendroglial cells during development.…”

Section: Discussionsupporting

confidence: 88%

Id2 and Id4 are not the major negative regulators of oligodendrocyte differentiation during early central nervous system development

Huang

et al. 2021

Glia

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Myelin sheathes ensure the rapid conduction of neural impulse and provide nutritional support for neurons. Myelin sheathes are formed by differentiated oligodendrocytes (OLs) in the central nervous system. During OL development, the differentiation of oligodendrocyte progenitor cells (OPCs) into mature OLs is controlled by both positive differentiation factors (drivers) and negative regulatory factors (brakes). Previous studies have suggested Id2 and Id4 as the key negative factors for OL differentiation. However, these conclusions were mainly based on in vitro studies and the reported OL phenotype in Id4 mutants appear to be mild. In this study, we systematically investigated the in vivo function of Id2 and Id4 genes in OL differentiation in their genetic mutants and in embryonic chicken spinal cord. Our results showed that disruption of Id4 has no effect on OL differentiation and maturation, whereas Id2 mutants and Id2/Id4 compound mutants display a mild and transient precocity of OL differentiation. In agreement with these loss-of-function studies, Id2, but not Id4, is weakly expressed in OPCs. Despite their minor roles in OL differentiation, forced expression of Id2 and Id4 in embryonic chicken spinal cords strongly inhibit the differentiation of OPCs. Taken together, our detailed functional and expressional studies strongly suggest that Id2 and Id4 are not the major in vivo repressors of OPC differentiation during animal development, shedding new light on the molecular regulation of early OL development.

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Section: Discussionsupporting

confidence: 88%

Id2 and Id4 are not the major negative regulators of oligodendrocyte differentiation during early central nervous system development

Huang

et al. 2021

Glia

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“…Several of these glial (progenitor) populations can be identified by expression of the transcription factors Id3, Sox9, Olig2, and NFIA. Previous studies in rodents showed that Id3 is only expressed in developing astrocytes (Lamantia, Tremblay, & Majewska, 2014;Molofsky et al, 2013). Sox9 is initially (E8.5-E18.5) expressed in all glial (precursor) cells, and is subsequently downregulated in myelinating oligodendrocytes (Stolt et al, 2003) and becomes astrocyte-specific (Sun et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

Affected astrocytes in the spinal cord of the leukodystrophy vanishing white matter

Leferink

Breeuwsma

Bugiani

et al. 2017

Glia

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Leukodystrophies are often devastating diseases, presented with progressive clinical signs as spasticity, ataxia and cognitive decline, and lack proper treatment options. New therapy strategies for leukodystrophies mostly focus on oligodendrocyte replacement to rescue lack of myelin in the brain, even though disease pathology also often involves other glial cells and the spinal cord. In this study we investigated spinal cord pathology in a mouse model for Vanishing White Matter disease (VWM) and show that astrocytes in the white matter are severely affected. Astrocyte pathology starts postnatally in the sensory tracts, followed by changes in the astrocytic populations in the motor tracts. Studies in post‐mortem tissue of two VWM patients, a 13‐year‐old boy and a 6‐year‐old girl, confirmed astrocyte abnormalities in the spinal cord. For proper development of new treatment options for VWM and, possibly, other leukodystrophies, future studies should investigate spinal cord involvement.

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“…These important observations confirmed Achúcarro and Río-Hortega's hypothesis that microglia are extremely dynamic (Achúcarro, 1909 ; Río-Hortega, 1919b ). The degree of their structural plasticity surpassed all expectations: microglial processes were found to survey their surrounding environment on a time scale of minutes, in contrast to neurons and other types of neuroglial cells which show no comparable structural remodeling in vivo (Majewska and Sur, 2003 ; Eom et al, 2011 ; Hughes et al, 2013 ; Lamantia et al, 2014 ). With these observations, microglia have emerged as the most dynamic cell type of the mature CNS.…”

Section: The Renaissance Of Functional Neuroanatomymentioning

confidence: 92%

From the Cajal alumni Achúcarro and Río-Hortega to the rediscovery of never-resting microglia

et al. 2015

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Under the guidance of Ramón y Cajal, a plethora of students flourished and began to apply his silver impregnation methods to study brain cells other than neurons: the neuroglia. In the first decades of the twentieth century, Nicolás Achúcarro was one of the first researchers to visualize the brain cells with phagocytic capacity that we know today as microglia. Later, his pupil Pío del Río-Hortega developed modifications of Achúcarro's methods and was able to specifically observe the fine morphological intricacies of microglia. These findings contradicted Cajal's own views on cells that he thought belonged to the same class as oligodendroglia (the so called “third element” of the nervous system), leading to a long-standing discussion. It was only in 1924 that Río-Hortega's observations prevailed worldwide, thus recognizing microglia as a unique cell type. This late landing in the Neuroscience arena still has repercussions in the twenty first century, as microglia remain one of the least understood cell populations of the healthy brain. For decades, microglia in normal, physiological conditions in the adult brain were considered to be merely “resting,” and their contribution as “activated” cells to the neuroinflammatory response in pathological conditions mostly detrimental. It was not until microglia were imaged in real time in the intact brain using two-photon in vivo imaging that the extreme motility of their fine processes was revealed. These findings led to a conceptual revolution in the field: “resting” microglia are constantly surveying the brain parenchyma in normal physiological conditions. Today, following Cajal's school of thought, structural and functional investigations of microglial morphology, dynamics, and relationships with neurons and other glial cells are experiencing a renaissance and we stand at the brink of discovering new roles for these unique immune cells in the healthy brain, an essential step to understand their causal relationship to diseases.

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Characterization of the BAC Id3-enhanced green fluorescent protein transgenic mouse line forin vivoimaging of astrocytes

Cited by 9 publications

References 54 publications

Id2 and Id4 are not the major negative regulators of oligodendrocyte differentiation during early central nervous system development

Id2 and Id4 are not the major negative regulators of oligodendrocyte differentiation during early central nervous system development

Affected astrocytes in the spinal cord of the leukodystrophy vanishing white matter

From the Cajal alumni Achúcarro and Río-Hortega to the rediscovery of never-resting microglia

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