Learn More
The potential role of doublecortin (Dcx), encoding a microtubule-associated protein, in brain development has remained controversial. Humans with mutations show profound alterations in cortical lamination, whereas in mouse, RNAi-mediated knockdown but not germline knockout shows abnormal positioning of cortical neurons. Here, we report that the(More)
The ability of the mature mammalian nervous system to continually produce neuronal precursors is of considerable importance, as manipulation of this process might one day permit the replacement of cells lost as a result of injury or disease. In mammals, the anterior subventricular zone (SVZa) region is one of the primary sites of adult neurogenesis. Here we(More)
Mutations in the doublecortin (DCX) gene in human or targeted disruption of the cdk5 gene in mouse lead to similar cortical lamination defects in the developing brain. Here we show that Dcx is phosphorylated by Cdk5. Dcx phosphorylation is developmentally regulated and corresponds to the timing of expression of p35, the major activating subunit for Cdk5.(More)
Humans with mutations in either DCX or LIS1 display nearly identical neuronal migration defects, known as lissencephaly. To define subcellular mechanisms, we have combined in vitro neuronal migration assays with retroviral transduction. Overexpression of wild-type Dcx or Lis1, but not patient-related mutant versions, increased migration rates. Dcx(More)
In comparison with other migratory cells, neurons exhibit a unique, highly polarized morphology and a distinctive pattern of movement. This migration consists of a repeating of three distinct phases: neurite outgrowth, movement of the centrosome into the leading process, and translocation of the nucleus towards the centrosome. The direction of movement is(More)
Humans with heterozygous inactivating mutations of the Lis1 gene display type I lissencephaly, a severe form of cortical dysplasia hypothesized to result from abnormal neuronal migration. Previously we reported the construction of an allelic series of the Lis1 gene in mice to analyze the effects of graded reduction of LIS1 protein on the pathogenesis of(More)
During brain development, neurons migrate great distances from proliferative zones to generate the cortical gray matter. A series of studies has identified genes that are critical for migration and targeting of neurons to specific brain regions. These genes encode three basic groups of proteins and produce three distinct phenotypes. The first group encodes(More)
The centrosome plays diverse roles throughout the cellular mitotic cycle and in post-mitotic cells. Analysis of centrosome position and dynamics in living murine cells has been limited due to a lack of adequate reporters and currently requires either cell fixation/immunostaining or transfection with centrosome reporters. Here we describe the generation and(More)
In this study, we surveyed central neurons that might be activated after peripheral administration of a gut-brain peptide ghrelin, by examining neurons expressing c-Fos protein. First, we examined the relationship between the dose of ghrelin and the amount of gastric acid secreted. Ghrelin induced a significant increase in the amount of gastric acid(More)
Ghrelin, a novel growth hormone-releasing peptide, is present in the rat and human stomach and is known to stimulate acid secretion and stomach motility. However, the mechanism of action of ghrelin is not fully understood. In the present study, we attempted to elucidate the role of histamine in ghrelin-induced acid secretion in rat stomach. Intravenous(More)