Altered Sensory Processing in the Somatosensory Cortex of the Mouse Mutant Barrelless

Welker, Egbert; Armstrong‐James, Michael; Bronchti, Gilles; Ourednik, W.; Gheorghita-Baechler, F.; Dubois, R.; Guernsey, Duane L.; Loos, H. Van der; Neumann, Paul E.

doi:10.1126/science.271.5257.1864

Cited by 132 publications

(155 citation statements)

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“…MAOA KO have a deletion of exons 2 and 3 in the gene encoding MAOA (Cases et al, 1996). The barrelless mouse strain (brl) is a spontaneous mutation that was identified as a loss of function of the adenylate cyclase-1 gene (Adcyl 1 brl ) due to the insertion of an early retrotransposon (Welker et al, 1996;Abdel-Majid et al, 1998). Reeler (Reln orl ) mice have a 220 nucleotide deletion in the 3Ј region of the Reelin transcript, resulting in a frame shift with the production of a predicted protein amputated of its C-terminal amino acids (de Bergeyck et al, 1997).…”

Section: Materials and Methods Animalsmentioning

confidence: 99%

“…Mice lacking the vesicular monoamine transporter (VMAT2 KO), the barrelless mutants (Adcyl 1 brl ), or the monoamine oxidase type A (MAOA KO) have an altered organization of the layer IV neurons, which are distributed as a continuous layer, instead of aggregating in barrels (Cases et al, 1996;Welker et al, 1996;Abdel-Majid et al, 1998;Alvarez et al, 2002). The Cux-1 and Cux-2 proteins were normally expressed in the upper cortical layers of VMAT2, barrelless, and MAOA KO mice (Fig.…”

Section: Cux-1 and Cux-2 Expression In Barrel-defective Micementioning

confidence: 99%

“…VMAT2 KO have a drastic reduction of monoaminergic neurotransmitters, serotonin, dopamine, and noradrenalin in the brain and display an altered organization of the layer IV neurons, although thalamocortical axons segregate almost normally (Alvarez et al, 2002). Adcyl 1 is expressed all along the primary sensory pathway (Nicol et al, 2005) and barrelless mice Adcyl 1 brl display a lack of segregation of both thalamocortical axons and cortical neurons (Welker et al, 1996). In these barrelless mutants, Cux-1 and Cux-2 IR display a normal laminar expression.…”

Section: Cux-1 and Cux-2 Expression In Mutants With An Altered Barrelmentioning

confidence: 99%

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Expression of Cux‐1 and Cux‐2 in the developing somatosensory cortex of normal and barrel‐defective mice

et al. 2006

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Recently, two orthologues of the Drosophila homeobox Cut gene, Cux-1 and Cux-2, have been identified as restricted molecular markers of upper layer (II-IV) neurons in the murine cerebral cortex. We show that during early postnatal life, from P0 to P10, Cux-1 and Cux-2 mRNA are coexpressed in all primary sensory cortices. Antisera to Cux-1 and Cux-2 immunoreactivities preferentially label neurons in the barrel walls of the primary somatosensory cortex (S1). Subsequently, Cux-1 remains enriched in sensory cortices, whereas Cux-2 expression enlarges to comprise the frontal and insular areas. The laminar distribution of Cux-1 and Cux-2 differs: Cux-1 follows a layer IV to layer II decreasing gradient of expression, whereas Cux-2 expression is homogeneous across layers IV-II. No colocalization was found with GABA and birth dating experiments showed that Cux-1-positive neurons in layer IV are born during a restricted period, E13.5-E14.5, suggesting that Cux-1 is a useful molecular marker of the glutamatergic neurons of layer IV. We examined Cux-1 and Cux-2 in barrel-defective mouse strains, the VMAT2 KO, the MAOA KO, and the Adcyl 1 brl strain. A normal expression level of Cux-1 and Cux-2 was found in layer IV, despite the lack of segregation of the neurons as barrels. Conversely, in Reeler mice, Cux-1 and Cux-2 had a distinct laminar distribution: the Cux-1-positive neurons had an inverted deep localization, whereas the Cux-2-positive neurons were distributed throughout the cortical thickness, suggesting that Cux-2 expression is more widely expressed in the inverted cortex of reeler mutants. Our results indicate that Cux-1 is a useful marker of the layer IV neurons in S1, and that Cux-1 and Cux-2 are differently regulated in the upper layers of the cerebral cortex.

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Section: Materials and Methods Animalsmentioning

confidence: 99%

Section: Cux-1 and Cux-2 Expression In Barrel-defective Micementioning

confidence: 99%

Section: Cux-1 and Cux-2 Expression In Mutants With An Altered Barrelmentioning

confidence: 99%

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Expression of Cux‐1 and Cux‐2 in the developing somatosensory cortex of normal and barrel‐defective mice

et al. 2006

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“…The first description of the phenotype was published recently (Welker et al 1996), and fewer than 2 years later it was mapped to a narrow zone on chromosome 11 (Abdel-Majid et al 1998) that was already known to contain six other genes. These six became plausible candidates for brl, and the search quickly narrowed to focus on the gene Adcy1, which codes for the enzyme adenylyl cyclase type I, an important part of an intracellular signalling pathway involving cyclic AMP (cAMP) in neurons.…”

Section: Targeted Mutationsmentioning

confidence: 99%

Single-Gene Influences on Brain and Behavior

Wahłsten

1999

Annu. Rev. Psychol.

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Abstract:As traditional behavioral genetics analysis merges with neurogenetics, the field of neurobehavioral genetics, focusing on single-gene effects, comes into being. New biotechnology has greatly accelerated gene discovery and the study of gene function in relation to brain and behavior. More than 7,000 genes in mice and 10,000 in humans have now been documented, and extensive information about the genetics of several species is readily available on the World Wide Web. Based on knowledge of the DNA sequence of a gene, a targeted mutation with the capacity to disable it can be created. These knockouts--also called null mutants--are employed in the study of a wide range of phenotypes, including learning and memory, appetite and obesity, and circadian rhythms. The era of examining single-gene effects from a reductionistic perspective is waning, and research with interacting arrays of genes in various environmental contexts is demonstrating a need for systems-oriented theory.

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“…The naturally occurring barrelless strain of mice harbors an inactivating mutation in the AC1 gene (1). These mice do not develop barrel structures, even though the size of their whisker representation is normal (40). Barrel structures are clusters of thalamocortical neurons in the somatosensory cortex that represent the receptive field of a single whisker.…”

Section: Ac1 and Ac8 Are Not Essential For Survival Of Micementioning

confidence: 99%

Why Calcium-Stimulated Adenylyl Cyclases?

2004

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(C1), another six-transmembrane domain (M2), and a cytoplasmic carboxy terminus of ~35 kDa (C2) (FIGURE 1B). The catalytic domain of adenylyl cyclases is hypothesized to be bipartite and split between C1 and C2 regions. The predicted size of mammalian adenylyl cyclases ranges from 110 to 130 kDa, but these proteins generally have an apparent molecular weight on SDS gels of ~200 kDa due to glycosylation in the extracellular loops of M1 and M2. Although the membrane topology and structure of adenylyl cyclases resemble transporters and ion channels, there is no evidence that these enzymes function as transporters or ion channels. However, cultured neurons express a voltage-sensitive adenylyl cyclase activity (25), suggesting that neurons contain an adenylyl cyclase or regulatory protein that is, like some ion channels, sensitive to membrane potential. AC1 is a Neurospecific Coincidence DetectorAC1 is the only neurospecific adenylyl cyclase identified thus far. It is expressed in brain, retina, and the adrenal medulla (45). Within the brain, AC1 is expressed in the hippocampus, neocortex, entorhinal cortex, cerebellar cortex, olfactory bulb, and pineal gland (29,45). AC1 expression in hippocampus increases dramatically during postnatal days 1-16 (31). The tissue specificity and developmentally regulated expression of the AC1 gene may be controlled by a 280-bp region and binary E-box like factor just 5Ј to the transcriptional start site (5). AC1 protein is detectable in the mossy fibers and the molecular layer of hippocampus and dentate in the macaque monkey, Macaca nemestrina (13), suggesting that AC1 is localized to axons in neurons of the hippocampus.Ca 2+ and CaM stimulate AC1 enzymatic activity with a half-maximal concentration of 150 nM free Ca 2+ , slightly above resting concentrations of Ca 2+ in neurons (43). CaM interacts with AC1 within the C1 loop region, close to the catalytic domain (43). The CaM-binding site within this region was identified by using peptide competitors and site-specifAdenylyl cyclases catalyze the conversion of ATP to cAMP, an important second messenger with diverse regulatory roles in the nervous system. Ten members of the adenylyl cyclase family have been identified by isolation of specific clones, each with unique regulatory properties and tissue distribution (for review see Ref. 46). In the brain, as in other tissues, adenylyl cyclases can be activated by receptor-coupled stimulatory G s proteins. For example, noradrenergic neurons of the locus ceruleus project to pyramidal neurons of the hippocampus and activate adenylyl cyclase through G s protein-coupled ␤-adrenergic receptors (FIGURE 1). Two of the adenylyl cyclases, AC1 and AC8, are activated by Ca 2+ through the Ca 2+ -binding protein calmodulin (CaM). This review focuses on the CaM-stimulated adenylyl cyclases and their role in neuronal signaling, synaptic plasticity, and memory formation. These enzymes link activitydependent increases in intracellular Ca 2+ to the production of intracellular cAMP. Isolation and Structure o...

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Altered Sensory Processing in the Somatosensory Cortex of the Mouse Mutant Barrelless

Cited by 132 publications

References 32 publications

Expression of Cux‐1 and Cux‐2 in the developing somatosensory cortex of normal and barrel‐defective mice

Expression of Cux‐1 and Cux‐2 in the developing somatosensory cortex of normal and barrel‐defective mice

Single-Gene Influences on Brain and Behavior

Why Calcium-Stimulated Adenylyl Cyclases?

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