Mapping Genes that Modulate Mouse Brain Development: A Quantitative Genetic Approach

Williams, Robert W.

doi:10.1007/978-3-540-48002-0_2

Cited by 108 publications

(90 citation statements)

References 94 publications

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“…Multiple experiments showed remarkable uniformity of slice acquisition from one sample to the next for a particular view. This is consistent with data showing that mice of the same age from inbred strains such as C57BL/6J have minimal interindividual variation in brain morphology (20).…”

supporting

confidence: 92%

“…Sections of the mouse brain are shown at ϳ0.8-mm intervals (mean Ϯ SE for both IA and Br: 0.83 Ϯ 0.14) proceeding (left to right, top to bottom) from IA ϩ4.18 mm, Br Ϫ0.38 mm to IA Ϫ1.66 mm, Br Ϫ5.46 mm (5,14,20). B: TH gene expression pattern warped onto mouse brain atlas sections (14,20). The level of expression is shown using a pseudocolor scale.…”

Section: Fig 2 Expression Pattern Of the Tyrosine Hydroxylase (Th)mentioning

confidence: 99%

“…The gene is also expressed in the hypothalamus (peri/paraventricular nuclei), zona incerta, median raphe nucleus, and locus coeruleus. The TH gene expression images were transformed into pseudocolor and warped onto corresponding sections of the mouse brain atlas (14,20) (Fig. 2B) to facilitate comparison with reconstructions obtained using GET.…”

Section: Fig 2 Expression Pattern Of the Tyrosine Hydroxylase (Th)mentioning

confidence: 99%

“…When the color had developed, sections were counterstained with nuclear Fast Red and coverslipped using Permount. To simplify comparison of the ␤-galactosidase staining with the GET reconstructions, the lacZ images were transformed into pseudocolor and warped onto corresponding sections of the mouse brain atlas (14,20). The warping was accomplished using our own implementation (web site below) of the thinplate splines warping method (1).…”

mentioning

confidence: 99%

“…The actual image was reconstructed by simply computing the inverse Fourier transform, i.e., ĝ (x,y,z) ϭ F Ϫ1 (G( x, y, z)). Image registration was performed using the Mouse Brain Library (14,20) and a widely employed atlas (5). For the purposes of presentation, C57BL/6J brain coronal sections from the Mouse Brain Library (14,20) were employed.…”

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confidence: 99%

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Gene expression tomography

Brown¹,

Ossadtchi

Ah³

et al. 2002

Physiological Genomics

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Gene expression tomography, or GET, is a new method to increase the speed of three-dimensional (3-D) gene expression analysis in the brain. The name is evocative of the method’s dual foundations in high-throughput gene expression analysis and computerized tomographic image reconstruction, familiar from techniques such as positron emission tomography (PET) and X-ray computerized tomography (CT). In GET, brain slices are taken using a cryostat in conjunction with axial rotation about independent axes to create a series of “views” of the brain. Gene expression information obtained from the axially rotated views can then be used to recreate 3-D gene expression patterns. GET was used to successfully reconstruct images of tyrosine hydroxylase gene expression in the mouse brain, using both RNase protection and real-time quantitative reverse transcription PCR (QRT-PCR). A Monte-Carlo analysis confirmed the good quality of the GET image reconstruction. By speeding acquisition of gene expression patterns, GET may help improve our understanding of the genomics of the brain in both health and disease.

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supporting

confidence: 92%

Section: Fig 2 Expression Pattern Of the Tyrosine Hydroxylase (Th)mentioning

confidence: 99%

Section: Fig 2 Expression Pattern Of the Tyrosine Hydroxylase (Th)mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Gene expression tomography

Brown¹,

Ossadtchi

Ah³

et al. 2002

Physiological Genomics

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Enhancement of human neural stem cell self‐renewal in 3D hypoxic culture

Ghourichaee

Powell

Leach

2016

Biotech & Bioengineering

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The pathology of neurological disorders is associated with the loss of neuronal and glial cells that results in functional impairments. Human neural stem cells (hNSCs), due to their self-renewing and multipotent characteristics, possess enormous tissue-specific regenerative potential. However, the efficacy of clinical applications is restricted due to the lack of standardized in vitro cell production methods with the capability of generating hNSC populations with well-defined cellular compositions. At any point, a population of hNSCs may include undifferentiated stem cells, intermediate and terminally differentiated progenies, and dead cells. Due to the plasticity of hNSCs, environmental cues play crucial roles in determining the cellular composition of hNSC cultures over time. Here, we investigated the independent and synergistic effect of three important environmental factors (i.e., culture dimensionality, oxygen concentration, and growth factors) on the survival, renewal potential, and differentiation of hNSCs. Our experimental design included two dimensional (2D) versus three dimensional (3D) cultures and normoxic (21% O ) versus hypoxic (3% O ) conditions in the presence and absence of epidermal growth factor (EGF) and fibroblast growth factor-2 (FGF-2). Additionally, we discuss the feasibility of mathematical models that predict hNSC growth and differentiation under these culture conditions by adopting a negative feedback regulatory term. Our results indicate that the synergistic effect of culture dimensionality and hypoxic oxygen concentration in the presence of growth factors enhances the proliferation of viable, undifferentiated hNSCs. Moreover, the same synergistic effect in the absence of growth factors promotes the differentiation of hNSCs. Biotechnol. Bioeng. 2017;114: 1096-1106. © 2016 Wiley Periodicals, Inc.

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Increased brain size and glial cell number in CD81‐null mice

Geisert

Williams

Geisert

et al. 2002

J of Comparative Neurology

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A key issue in the development of the central nervous system (CNS) is understanding the molecular mechanisms regulating cell number. The present study examines the role of CD81 (previously known as TAPA, the target of the antiproliferative antibody) in the control of brain size and glial cell number. CD81 is a member of the tetraspanin family of proteins. This group of small membrane proteins is associated with the regulation of cell migration and mitotic activity. Glial cells express CD81, and antibodies directed against this protein suppress the mitotic activity of cultured cells. In this study, we examine the effects of the CD81 -/- mutation on the CNS of mature mice. These mice have extremely large brains, as much as 30% larger than the brains of wild-type (+/+) littermates. The increase in brain weight is accompanied by an increase in the number astrocytes and microglia, whereas the number of neurons and oligodendrocytes in the CD81 -/- animals appears to be normal. When the CD81 -/- mutation is placed on different genetic backgrounds, there is a remarkable range in the penetrance of the null allele phenotype, demonstrating that the mutation can be affected by modifier loci. This work provides support for the role of CD81 in the regulation of astrocyte and microglial number, perhaps by regulating cell proliferation by a contact inhibition-dependent mechanism.

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Mapping Genes that Modulate Mouse Brain Development: A Quantitative Genetic Approach

Cited by 108 publications

References 94 publications

Gene expression tomography

Gene expression tomography

Enhancement of human neural stem cell self‐renewal in 3D hypoxic culture

Increased brain size and glial cell number in CD81‐null mice

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