Cell-type-specific neuroanatomy of cliques of autism-related genes in the mouse brain

Grange, Pascal; Menashe, Idan; Hawrylycz, Michael

doi:10.3389/fncom.2015.00055

Cited by 5 publications

(5 citation statements)

References 59 publications

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“…Interestingly, many of the monogenic, mendelian-inherited ASD genes have a high coexpression in the cerebellum. This growing list of genes includes, but is not limited to, SHANK2 and SHANK3, TSC1 and TSC2, and AUTS2 [4][5][6].…”

Section: Introductionmentioning

confidence: 99%

Abnormal Cerebellar Development in Autism Spectrum Disorders

2021

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Autism spectrum disorders (ASD) comprise a group of heterogeneous neurodevelopmental conditions characterized by impaired social interactions and repetitive behaviors with symptom onset in early infancy. The genetic risks for ASD have long been appreciated: concordance of ASD diagnosis may be as high as 90% for monozygotic twins and 30% for dizygotic twins, and hundreds of mutations in single genes have been associated with ASD. Nevertheless, only 5–30% of ASD cases can be explained by a known genetic cause, suggesting that genetics is not the only factor at play. More recently, several studies reported that up to 40% of infants with cerebellar hemorrhages and lesions are diagnosed with ASD. These hemorrhages are overrepresented in severely premature infants, who are born during a period of highly dynamic cerebellar development that encompasses an approximately 5-fold size expansion, an increase in structural complexity, and remarkable rearrangements of local neural circuits. The incidence of ASD-causing cerebellar hemorrhages during this window supports the hypothesis that abnormal cerebellar development may be a primary risk factor for ASD. However, the links between developmental deficits in the cerebellum and the neurological dysfunctions underlying ASD are not completely understood. Here, we discuss key processes in cerebellar development, what happens to the cerebellar circuit when development is interrupted, and how impaired cerebellar function leads to social and cognitive impairments. We explore a central question: Is cerebellar development important for the generation of the social and cognitive brain or is the cerebellum part of the social and cognitive brain itself?

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Section: Introductionmentioning

confidence: 99%

Abnormal Cerebellar Development in Autism Spectrum Disorders

2021

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“…For the rest of the genome the brain was sliced sagitally, and only the left hemisphere was processed (giving rise to the sagittal ABA). In the computational approaches of [19,9,5,6,20,7], only data from the coronal ABA were analyzed, in order to obtain brain-wide results. However, these brain-wide results revealed a large degree of left-right symmetry.…”

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confidence: 99%

Cell-type-specific computational neuroanatomy, simulations from the sagittal and coronal Allen Brain Atlas

Grange¹

2015

Preprint

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The Allen Atlas of the adult mouse brain is a brain-wide, genome-wide data set that has been made available online, triggering a renaissance in neuroanatomy. In particular, it has been used to define brain regions in a computational, data-driven way, and to estimate the region-specificity of cell types characterized independently by their transcriptional activity. However, these results were based on one series of co-registered (coronal) ISH image series per gene, whereas the online ABA contains several image series per genes, including sagittal ones. Since the sagittal series cover mostly the left hemisphere, we can simulate the variability of results by repeatedly drawing a random image series for each gene and restricting the computation to the left hemisphere. This gives rise to an estimate of error bars on the results of computational neuroanatomy. This manuscript is a complement to the paper Computational neuroanatomy: mapping cell-type densities in the mouse brain, simulations from the Allen Brain Atlas prepared for the International Conference on Mathematical Modeling in Physical Sciences June 5-8,

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“…Loops that are as persistent as the cortico-striatal ones yield natural candidates for places where to look for such genetic signatures of functional networks. Moreover, the brain-wide coverage of the gene-expression atlas [25,26] allows to estimate spatial densities of cell types known by their transcriptional activity [29,30,33], which yields neuroanatomical predictions relevant to brain disorders [31,32]. The present work could lead to insights into the correlation structure between the local density of loops and the spatial density of cell types.…”

Section: Brain-wide Density Of Connections By Loops To a Given Regionmentioning

confidence: 87%

Topology of the mesoscale connectome of the mouse brain

Grange

2020

Computational and Mathematical Biophysics

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The wiring diagram of the mouse brain has recently been mapped at a mesoscopic scale in the Allen Mouse Brain Connectivity Atlas. Axonal projections from brain regions were traced using green fluoresent proteins. The resulting data were registered to a common three-dimensional reference space. They yielded a matrix of connection strengths between 213 brain regions. Global features such as closed loops formed by connections of similar intensity can be inferred using tools from persistent homology. We map the wiring diagram of the mouse brain to a simplicial complex (filtered by connection strengths). We work out generators of the first homology group. Some regions, including nucleus accumbens, are connected to the entire brain by loops, whereas no region has non-zero connection strength to all brain regions. Thousands of loops go through the isocortex, the striatum and the thalamus. On the other hand, medulla is the only major brain compartment that contains more than 100 loops.

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Cell-type-specific neuroanatomy of cliques of autism-related genes in the mouse brain

Cited by 5 publications

References 59 publications

Abnormal Cerebellar Development in Autism Spectrum Disorders

Abnormal Cerebellar Development in Autism Spectrum Disorders

Cell-type-specific computational neuroanatomy, simulations from the sagittal and coronal Allen Brain Atlas

Topology of the mesoscale connectome of the mouse brain

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