Talk:Neural - Cerebellum Development: Difference between revisions
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The definition of Purkinje cell zones by their white matter compartments, their physiological properties, and their molecular identity and the birthdate of their Purkinje cells will be reviewed. | The definition of Purkinje cell zones by their white matter compartments, their physiological properties, and their molecular identity and the birthdate of their Purkinje cells will be reviewed. | ||
PMID 22396330 | PMID 22396330 | ||
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3359460 | |||
==2011== | ==2011== | ||
Revision as of 18:41, 20 September 2012
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Cite this page: Hill, M.A. (2024, May 8) Embryology Neural - Cerebellum Development. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Talk:Neural_-_Cerebellum_Development |
2012
A note on the definition and the development of cerebellar Purkinje cell zones
Cerebellum. 2012 Jun;11(2):422-5.
Voogd J. Source Dept. of Neuroscience, Erasmus Medical Center, Rotterdam, The Netherlands. janvoogd@bart.nl Abstract
The definition of Purkinje cell zones by their white matter compartments, their physiological properties, and their molecular identity and the birthdate of their Purkinje cells will be reviewed.
PMID 22396330
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3359460
2011
Cerebellum development and medulloblastoma
Curr Top Dev Biol. 2011;94:235-82.
Roussel MF, Hatten ME. Source Department of Tumor Cell Biology and Genetics, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Abstract
In the last 20 years, it has become clear that developmental genes and their regulators, noncoding RNAs including microRNAs and long-noncoding RNAs, within signaling pathways play a critical role in the pathogenesis of cancer. Many of these pathways were first identified in genetic screens in Drosophila and other lower organisms. Mammalian orthologs were subsequently identified and genes within the pathways cloned and found to regulate cell growth. Genes and pathways expressed during embryonic development, including the Notch, Wnt/β-Catenin, TGF-β/BMP, Shh/Patched, and Hippo pathways are mutated, lost, or aberrantly regulated in a wide variety of human cancers, including skin, breast, blood, and brain cancers, including medulloblastoma. These biochemical pathways affect cell fate determination, axis formation, and patterning during development and regulate tissue homeostasis and regeneration in adults. Medulloblastoma, the most common malignant nervous system tumor in childhood, are thought to arise from disruptions in cerebellar development [reviewed by Marino, S. (2005)]. Defining the extracellular cues and intracellular signaling pathways that control cerebellar neurogenesis, especially granule cell progenitor (GCP) proliferation and differentiation has been useful for developing models to unravel the mechanisms underlying medulloblastoma formation and growth. In this chapter, we will review the development of the cerebellar cortex, highlighting signaling pathways of potential relevance to tumorigenesis. Copyright © 2011 Elsevier Inc. All rights reserved.
PMID 21295689
Preterm delivery disrupts the developmental program of the cerebellum
PLoS One. 2011;6(8):e23449. Epub 2011 Aug 17.
Haldipur P, Bharti U, Alberti C, Sarkar C, Gulati G, Iyengar S, Gressens P, Mani S. Source National Brain Research Centre, Manesar, Haryana, India.
Abstract
A rapid growth in human cerebellar development occurs in the third trimester, which is impeded by preterm delivery. The goal of this study was to characterize the impact of preterm delivery on the developmental program of the human cerebellum. Still born infants, which meant that all development up to that age had taken place in-utero, were age paired with preterm delivery infants, who had survived in an ex-utero environment, which meant that their development had also taken place outside the uterus. The two groups were assessed on quantitative measures that included molecular markers of granule neuron, purkinje neuron and bergmann glia differentiation, as well as the expression of the sonic hedgehog signaling pathway, that is important for cerebellar growth. We report that premature birth and development in an ex-utero environment leads to a significant decrease in the thickness and an increase in the packing density of the cells within the external granular layer and the inner granular layer well, as a reduction in the density of bergmann glial fibres. In addition, this also leads to a reduced expression of sonic hedgehog in the purkinje layer. We conclude that the developmental program of the cerebellum is specifically modified by events that follow preterm delivery.
PMID 21858122
Alcohol exposure decreases CREB binding protein expression and histone acetylation in the developing cerebellum
PLoS One. 2011;6(5):e19351. Epub 2011 May 31.
Guo W, Crossey EL, Zhang L, Zucca S, George OL, Valenzuela CF, Zhao X. Source Department of Neurosciences, University of New Mexico School of Medicine, Albuquerque, New Mexico, United States of America.
Abstract
BACKGROUND: Fetal alcohol exposure affects 1 in 100 children making it the leading cause of mental retardation in the US. It has long been known that alcohol affects cerebellum development and function. However, the underlying molecular mechanism is unclear.
METHODOLOGY/PRINCIPAL FINDINGS: We demonstrate that CREB binding protein (CBP) is widely expressed in granule and Purkinje neurons of the developing cerebellar cortex of naïve rats. We also show that exposure to ethanol during the 3(rd) trimester-equivalent of human pregnancy reduces CBP levels. CBP is a histone acetyltransferase, a component of the epigenetic mechanism controlling neuronal gene expression. We further demonstrate that the acetylation of both histone H3 and H4 is reduced in the cerebellum of ethanol-treated rats.
CONCLUSIONS/SIGNIFICANCE: These findings indicate that ethanol exposure decreases the expression and function of CBP in the developing cerebellum. This effect of ethanol may be responsible for the motor coordination deficits that characterize fetal alcohol spectrum disorders.
PMID 21655322
The p53 inhibitor MDM2 facilitates Sonic Hedgehog-mediated tumorigenesis and influences cerebellar foliation
PLoS One. 2011 Mar 18;6(3):e17884.
Malek R, Matta J, Taylor N, Perry ME, Mendrysa SM. Source Department of Basic Medical Sciences, School of Veterinary Medicine, Purdue University, West Lafayette, Indiana, United States of America.
Abstract
Disruption of cerebellar granular neuronal precursor (GNP) maturation can result in defects in motor coordination and learning, or in medulloblastoma, the most common childhood brain tumor. The Sonic Hedgehog (Shh) pathway is important for GNP proliferation; however, the factors regulating the extent and timing of GNP proliferation, as well as GNP differentiation and migration are poorly understood. The p53 tumor suppressor has been shown to negatively regulate the activity of the Shh effector, Gli1, in neural stem cells; however, the contribution of p53 to the regulation of Shh signaling in GNPs during cerebellar development has not been determined. Here, we exploited a hypomorphic allele of Mdm2 (Mdm2(puro)), which encodes a critical negative regulator of p53, to alter the level of wild-type MDM2 and p53 in vivo. We report that mice with reduced levels of MDM2 and increased levels of p53 have small cerebella with shortened folia, reminiscent of deficient Shh signaling. Indeed, Shh signaling in Mdm2-deficient GNPs is attenuated, concomitant with decreased expression of the Shh transducers, Gli1 and Gli2. We also find that Shh stimulation of GNPs promotes MDM2 accumulation and enhances phosphorylation at serine 166, a modification known to increase MDM2-p53 binding. Significantly, loss of MDM2 in Ptch1(+/-) mice, a model for Shh-mediated human medulloblastoma, impedes cerebellar tumorigenesis. Together, these results place MDM2 at a major nexus between the p53 and Shh signaling pathways in GNPs, with key roles in cerebellar development, GNP survival, cerebellar foliation, and MB tumorigenesis.
PMID 21437245
Development of axon-target specificity of ponto-cerebellar afferents
PLoS Biol. 2011 Feb 8;9(2):e1001013.
Kalinovsky A, Boukhtouche F, Blazeski R, Bornmann C, Suzuki N, Mason CA, Scheiffele P. Source Department of Physiology & Cellular Biophysics and Department of Neuroscience, Columbia University, New York, New York, United States of America.
Abstract
The function of neuronal networks relies on selective assembly of synaptic connections during development. We examined how synaptic specificity emerges in the pontocerebellar projection. Analysis of axon-target interactions with correlated light-electron microscopy revealed that developing pontine mossy fibers elaborate extensive cell-cell contacts and synaptic connections with Purkinje cells, an inappropriate target. Subsequently, mossy fiber-Purkinje cell connections are eliminated resulting in granule cell-specific mossy fiber connectivity as observed in mature cerebellar circuits. Formation of mossy fiber-Purkinje cell contacts is negatively regulated by Purkinje cell-derived BMP4. BMP4 limits mossy fiber growth in vitro and Purkinje cell-specific ablation of BMP4 in mice results in exuberant mossy fiber-Purkinje cell interactions. These findings demonstrate that synaptic specificity in the pontocerebellar projection is achieved through a stepwise mechanism that entails transient innervation of Purkinje cells, followed by synapse elimination. Moreover, this work establishes BMP4 as a retrograde signal that regulates the axon-target interactions during development.
PMID 21346800 [PubMed - indexed for MEDLINE] PMCID PMC3035609
