Automatic recognition and statistical quantification of spatial patterns of gene expression in zebra finch brain in response to auditory stimulation

AbstractNeurodevelopmental disorders are highly heritable and associated with spatially-selective disruptions of brain anatomy. The logic that translates genetic risks into spatially patterned brain vulnerabilities remains unclear but is a fundamental question in disease pathogenesis. Here, we approach this question by integrating (i) in vivo neuroimaging data from patient subgroups with known causal genomic copy number variations (CNVs), and (ii) bulk and single-cell gene expression data from healthy cortex. First, for each of six different CNV disorders, we show that spatial patterns of cortical anatomy change in youth are correlated with spatial patterns of expression for CNV region genes in bulk cortical tissue from typically-developing adults. Next, by transforming normative bulk-tissue cortical expression data into cell-type expression maps, we further link each disorder’s anatomical change map to specific cell classes and specific CNV-region genes that these cells express. Finally, we establish convergent validity of this “transcriptional vulnerability model” by inter-relating patient neuroimaging data with measures of altered gene expression in both brain and blood-derived patient tissue. Our work clarifies general biological principles that govern the mapping of genetic risks onto regional brain disruption in neurodevelopmental disorders. We present new methods that can harness these principles to screen for potential cellular and molecular determinants of disease from readily available patient neuroimaging data.

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Ontogenic regulation of spatial differentiation in the crypt-villus axis of normal and isografted small intestine

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1995.269.4.g500 ◽

1995 ◽

Vol 269 (4) ◽

pp. G500-G511 ◽

Cited By ~ 1

Author(s):

E. D. Gutierrez ◽

K. J. Grapperhaus ◽

D. C. Rubin

Keyword(s):

Gene Expression ◽

Spatial Patterns ◽

Spatial Differentiation ◽

Vertical Axis ◽

Fetal Life ◽

Mrna Levels ◽

Fatty Acid Binding ◽

Extracellular Substances ◽

Enterocytic Differentiation

Despite rapid proliferation, the mammalian intestinal epithelium maintains precise spatial differentiation from crypt to villus tip and from duodenum to colon. During perinatal life, the rodent gut undergoes a dramatic morphogenesis, resulting in formation of the crypt-villus and duodenal-colonic axes. The ontogeny of regional differences in gene expression in the emerging vertical axis has not been well described. We used the liver fatty acid binding protein (L-FABP) and apolipoprotein (apo) AIV genes as markers of neonatal enterocytic differentiation. In situ hybridization analyses revealed that both genes exhibit unique spatial patterns of expression along the jejunal crypt-villus axis during ontogeny, characterized by increased cellular mRNA levels in villus base enterocytes. To examine the requirement for a normal luminal environment to generate these precise patterns of cellular gene expression, we employed intestinal isograft techniques. Fetal intestines were implanted as early as embryonic day 12. Appropriate expression of the apo AIV and L-FABP genes was recapitulated during villus morphogenesis in fetal life. However, spatial patterns of gene expression in the isografted postnatal cryptvillus axis were altered. The preferential accumulation of L-FABP and apo AIV mRNA in villus base enterocytes was never observed in isografts. These results suggest that a “basal” differentiation program is encoded in fetal endoderm and mesenchyme, yet extracellular substances contained in the lumen or extrinsic to the intestine play an important modulatory role in generating spatial differentiation during ontogeny.

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Transposable elements generate novel spatial patterns of gene expression in antirrhinum majus

Cell ◽

10.1016/0092-8674(86)90451-4 ◽

1986 ◽

Vol 47 (2) ◽

pp. 285-296 ◽

Cited By ~ 143

Author(s):

Enrico S. Coen ◽

Rosemary Carpenter ◽

Cathie Martin

Keyword(s):

Gene Expression ◽

Transposable Elements ◽

Spatial Patterns ◽

Antirrhinum Majus

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Spatial Patterns of Arylsulfatase mRNA Expression in Sea Urchin Embryo. (arylsulfatase/sea urchin embryo/gene expression)

Development Growth & Differentiation ◽

10.1111/j.1440-169x.1990.00009.x ◽

1990 ◽

Vol 32 (1) ◽

pp. 9-13 ◽

Cited By ~ 29

Author(s):

Koji Akasaka ◽

Takayuki Ueda ◽

Toru Higashinakagawa ◽

Kazumi Yamada ◽

Hiraku Shimada

Keyword(s):

Gene Expression ◽

Mrna Expression ◽

Spatial Patterns ◽

Sea Urchin ◽

Sea Urchin Embryo

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The Dynamic DNA Demethylation during Postnatal Neuronal Development and Neural Stem Cell Differentiation

Stem Cells International ◽

10.1155/2018/2186301 ◽

2018 ◽

Vol 2018 ◽

pp. 1-10 ◽

Cited By ~ 4

Author(s):

Huikang Tao ◽

Pei Xie ◽

Yuhang Cao ◽

Liqi Shu ◽

Liping Li ◽

...

Keyword(s):

Gene Expression ◽

Spatial Patterns ◽

Neuronal Development ◽

Stem Cell Differentiation ◽

Brain Regions ◽

Dna Demethylation ◽

Dynamic Features ◽

Dot Blot ◽

Temporal And Spatial Patterns ◽

Temporal And Spatial

Background. DNA demethylation, the conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC), plays important roles in diverse biological processes and multiple diseases by regulating gene expression. Methods. In this study, utilizing DNA dot blot, immunofluorescence staining, and qRT-PCR, we studied the expression pattern of Tets, the enzymes governing DNA demethylation, and the levels of 5hmC, 5fC, and 5caC during the postnatal neuronal development of mice. Results. It was found that 5hmC, 5fC, and 5caC were highly enriched in multiple brain regions and aNSCs and displayed temporal and spatial patterns during postnatal neuronal development and the differentiation of aNSCs. Consistently, the expression of Tets also exhibited temporal and spatial patterns. Conclusion. DNA demethylation displayed dynamic features during postnatal neuronal development and the differentiation of aNSCs of mice, which could contribute to appropriate gene expression.

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