Cellular distribution of the fragile X mental retardation protein in the mouse brain

Zorio, Diego A. R.; Jackson, Christine E.; Liu, Yong; Rubel, Edwin W.; Wang, Yuan

doi:10.1002/cne.24100

Cited by 58 publications

(59 citation statements)

References 90 publications

(128 reference statements)

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“…Recent cellular analyses, however, reported strong expression of FMRP in auditory brainstem cell groups across a number of vertebrate species . Quantitative analyses across the entire adult (5‐6 weeks) mouse brain further confirmed that auditory neurons in the brainstem and thalamus have levels of FMRP immunoreactivity comparable to those in cortical neurons . It is worth noting that FMRP is also expressed in spiral ganglion neurons, which convey acoustic signals from the inner ear to the brainstem, in both birds and mammals.…”

Section: Fmrp Regulates the Development Of Synaptic Transmission In Tmentioning

confidence: 86%

“…It is worth noting that FMRP is also expressed in spiral ganglion neurons, which convey acoustic signals from the inner ear to the brainstem, in both birds and mammals. In contrast, many cell groups in the midbrain and hypothalamus exhibit low FMRP levels …”

Section: Fmrp Regulates the Development Of Synaptic Transmission In Tmentioning

confidence: 95%

“…27 Quantitative analyses across the entire adult (5-6 weeks) mouse brain further confirmed that auditory neurons in the brainstem and thalamus have levels of FMRP immunoreactivity comparable to those in cortical neurons. 28 It is worth noting that FMRP is also expressed in spiral ganglion neurons, which convey acoustic signals from the inner ear to the brainstem, in both birds and mammals. In contrast, many cell groups in the midbrain and hypothalamus exhibit low FMRP levels.…”

Section: Development Of Synaptic Transmission In the Auditory Brainstemmentioning

confidence: 99%

“…In contrast, many cell groups in the midbrain and hypothalamus exhibit low FMRP levels. 28 In this section, we first describe the expression and function of FMRP in the ITD circuit (3.1) and then discuss how Fmr1 deletion affects the cell groups involved in ILD computation (3.2). Finally, we summarize effects of FMRP loss on auditory brainstem responses (ABRs), a noninvasive physiological output of the auditory brainstem (3.3).…”

Section: Development Of Synaptic Transmission In the Auditory Brainstemmentioning

confidence: 99%

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Mechanisms underlying auditory processing deficits in Fragile X syndrome

et al. 2020

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Autism spectrum disorders (ASD) are strongly associated with auditory hypersensitivity or hyperacusis (difficulty tolerating sounds). Fragile X syndrome (FXS), the most common monogenetic cause of ASD, has emerged as a powerful gateway for exploring underlying mechanisms of hyperacusis and auditory dysfunction in ASD. This review discusses examples of disruption of the auditory pathways in FXS at molecular, synaptic, and circuit levels in animal models as well as in FXS individuals. These examples highlight the involvement of multiple mechanisms, from aberrant synaptic development and ion channel deregulation of auditory brainstem circuits, to impaired neuronal plasticity and network hyperexcitability in the auditory cortex. Though a relatively new area of research, recent discoveries have increased interest in auditory dysfunction and mechanisms underlying hyperacusis in this disorder. This rapidly growing body of data has yielded novel research directions addressing critical questions regarding the timing and possible outcomes of human therapies for auditory dysfunction in ASD.

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Section: Fmrp Regulates the Development Of Synaptic Transmission In Tmentioning

confidence: 86%

Section: Fmrp Regulates the Development Of Synaptic Transmission In Tmentioning

confidence: 95%

Section: Development Of Synaptic Transmission In the Auditory Brainstemmentioning

confidence: 99%

Section: Development Of Synaptic Transmission In the Auditory Brainstemmentioning

confidence: 99%

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Mechanisms underlying auditory processing deficits in Fragile X syndrome

et al. 2020

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“…This pattern of results suggests that loss of FMRP leads to variable outcomes on white matter circuitry, consistent with evidence that the protein is expressed differentially across brain regions and over time 39 and is pronounced in subcortical sensory and motor cells. 40 …”

Section: Discussionmentioning

confidence: 99%

Development of White Matter Circuitry in Infants With Fragile X Syndrome

Swanson¹,

Wolff

Shen³

et al. 2018

JAMA Psychiatry

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IMPORTANCE Fragile X syndrome (FXS) is a genetic neurodevelopmental disorder and the most common inherited cause of intellectual disability in males. However, there are no published data on brain development in children with FXS during infancy. OBJECTIVE To characterize the development of white matter at ages 6, 12, and 24 months in infants with FXS compared with that of typically developing controls. DESIGN, SETTING, AND PARTICIPANTS Longitudinal behavioral and brain imaging data were collected at 1 or more time points from 27 infants with FXS and 73 typically developing controls between August 1, 2008, and June 14, 2016, at 2 academic medical centers. Infants in the control group had no first- or second-degree relatives with intellectual or psychiatric disorders, including FXS and autism spectrum disorder. MAIN OUTCOMES AND MEASURES Nineteen major white matter pathways were defined in common atlas space based on anatomically informed methods. Diffusion parameters, including fractional anisotropy, were compared between groups using linear mixed effects modeling. Fiber pathways showing group differences were subsequently examined in association with direct measures of verbal and nonverbal development. RESULTS There were significant differences in the development of 12 of 19 fiber tracts between the 27 infants with FXS (22 boys and 5 girls) and the 73 infants in the control group (46 boys and 27 girls), with lower fractional anisotropy in bilateral subcortical-frontal, occipital-temporal, temporal-frontal, and cerebellar-thalamic pathways, as well as 4 of 6 subdivisions of the corpus callosum. For all 12 of these pathways, there were significant main effects between groups but not for the interaction of age × group, indicating that lower fractional anisotropy was present and stable from age 6 months in infants with FXS. Lower fractional anisotropy values in the uncinate fasciculi were correlated with lower nonverbal developmental quotient in the FXS group (left uncinate, F = 10.06; false discovery rate–corrected P = .03; right uncinate, F = 21.8; P = .004). CONCLUSIONS AND RELEVANCE The results substantiate in human infants the essential role of fragile X gene expression in the early development of white matter. The findings also suggest that the neurodevelopmental effects of FXS are well established at 6 months of age.

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Axonal localization of the fragile X family of RNA binding proteins is conserved across mammals

Shepard

Korsak

DeBartolo

et al. 2019

J of Comparative Neurology

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Spatial segregation of proteins to neuronal axons arises in part from local translation of mRNAs that are first transported into axons in ribonucleoprotein particles (RNPs), complexes containing mRNAs and RNA binding proteins. Understanding the importance of local translation for a particular circuit requires not only identifying axonal RNPs and their mRNA cargoes, but also whether these RNPs are broadly conserved or restricted to only a few species. Fragile X granules (FXGs) are axonal RNPs containing the fragile X related family of RNA binding proteins along with ribosomes and specific mRNAs. FXGs were previously identified in mouse, rat, and human brains in a conserved subset of neuronal circuits but with species-dependent developmental profiles. Here, we asked whether FXGs are a broadly conserved feature of the mammalian brain and sought to better understand the species-dependent developmental expression pattern. We found FXGs in a conserved subset of neurons and circuits in the brains of every examined species that together include mammalian taxa separated by up to 160 million years of divergent evolution. A developmental analysis of rodents revealed that FXG expression in frontal cortex and olfactory bulb followed consistent patterns in all species examined. In contrast, FXGs in hippocampal mossy fibers increased in abundance across development for most species but decreased across development in guinea pigs and members of the Mus genus, animals that navigate particularly small home ranges in the wild. The widespread conservation of FXGs suggests that axonal translation is an ancient, conserved mechanism for regulating the proteome of mammalian axons. K E Y W O R D S axonal translation, local protein synthesis, RNA binding proteins, RRID AB_10805421, RRID AB_2278530, RRID AB_2737297, RRID AB_528262

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Cellular distribution of the fragile X mental retardation protein in the mouse brain

Cited by 58 publications

References 90 publications

Mechanisms underlying auditory processing deficits in Fragile X syndrome

Mechanisms underlying auditory processing deficits in Fragile X syndrome

Development of White Matter Circuitry in Infants With Fragile X Syndrome

Axonal localization of the fragile X family of RNA binding proteins is conserved across mammals

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