Linkage and physical mapping of X-linked lissencephaly/SBH (XLIS): a gene causing neuronal migration defects in human brain

Ross, M. Elizabeth; Allen, Kristina M.; Srivastava, Anand; Featherstone, T.; Gleeson, Joseph G.; Hirsch, Betsy A.; Harding, Brian; Andermann, Eva; Abdullah, Rabi; Berg, Michael J.; Czapansky-Bielman, Désirée; Flanders, Dean; Guerrini, Renzo; Motté, Jacques; Mira, Alberto; Scheffer, Ingrid E.; Berkovic, Samuel F.; Salvatore, Francesco; King, Richard A.; Ledbetter, David H.; Schlessinger, David; Dobyns, William B.; Walsh, Christopher A.

doi:10.1093/hmg/6.4.555

Cited by 90 publications

(60 citation statements)

References 36 publications

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“…DCX is expressed in migrating neurons throughout the central and peripheral nervous system during embryonic and postnatal development (23). DCX is up-regulated in subventricular zone cells after severe ischemic insult, in vivo and in vitro (16).…”

Section: Resultsmentioning

confidence: 99%

Ectopic Doublecortin Gene Expression Suppresses the Malignant Phenotype in Glioblastoma Cells

Santra¹,

Zhang²,

Santra³

et al. 2006

Cancer Research

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Doublecortin (DCX) is one of the three genes found from Affymetrix gene chip analysis related to glioma patient survival. Two other genes (e.g., osteonectin and semaphorin 3B) are well characterized as antioncogenic and tumor suppressor genes. However, there is no report about the involvement of DCX in cancer. Here, we show that gene transfer technology into DCX-deficient glioblastoma cell lines, such as A172, U87, U251N, RG2, and 9L, with DCX cDNA significantly suppressed growth of these glioma cells. U87 cells with ectopic expression of DCX exhibit a marked suppression of the transformed phenotype as growth arrested in the G 2 phase of the cell cycle progression, small colony formation in soft agar, and no tumor formation in nude rats. This transformed phenotype can be restored by knocking down DCX expression with DCX small interfering RNA. DCX was highly phosphorylated in glioma cells. Phosphorylation in the glioma cells was greater than in noncancer cells such as mouse NIH 3T3 and human embryonic kidney 293T cells. Coimmunoprecipitation of the phosphorylated DCX and spinophilin/neurabin II from DCX-synthesizing glioma cells indicated their interaction. This interaction would lead to a block of anchorage-independent growth as neurabin II is a synergistic inhibitor of anchorage-independent growth with p14ARF (ARF). Interaction between phosphorylated DCX and neurabin II may induce the association of the protein phosphatase 1 catalytic subunit (PP1) with neurabin II and inactivate PP1 and block mitosis during G 2 and M phases of the cell cycle progression. Thus, DCX seems to be a tumor suppressor of glioma. (Cancer Res 2006; 66(24): 11726-35)

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Section: Resultsmentioning

confidence: 99%

Ectopic Doublecortin Gene Expression Suppresses the Malignant Phenotype in Glioblastoma Cells

Santra¹,

Zhang²,

Santra³

et al. 2006

Cancer Research

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“…The LIS1 protein regulates microtubule function and plateletactivating factor acetylhydrolase activity (reviewed in 6). A second lissencephaly type I gene mapped to the X chromosome (7,8), was cloned and termed doublecortin (DCX) (9,10). Mutations in the X-linked DCX gene result in lissencephaly in males or subcortical laminar heterotopia (SCLH), i.e.…”

Section: Introductionmentioning

confidence: 99%

DCX in PC12 cells: CREB-mediated transcription and neurite outgrowth

Shmueli

Gdalyahu²,

Sorokina³

et al. 2001

Human Molecular Genetics

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Mutations in doublecortin (DCX) result in X-linked lissencephaly in males. To explore the role of DCX in differentiation and signal transduction we overexpressed DCX in PC12 cells. Our results indicate that DCX stabilizes microtubules and inhibits neurite outgrowth in nerve growth factor-induced differentiation. However, neurite length is increased when differentiation is induced by epidermal growth factor and forskolin or by dibutyryl-cAMP. Furthermore, CREB-mediated transcription is downregulated, supporting the notion that cytoskeletal regulatory proteins can affect the transcriptional state of a cell. Using different constructs and mutations we reach the conclusion that microtubule stabilization is a key factor, but not the only one, in controlling neurite extension. Overexpression of a mutation found in a lissencephaly patient (S47R), completely blocks neurite outgrowth. We propose that these functions are important during normal and abnormal brain development.

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“…Among those without such a deletion, 40% have a mutation or an intragenic deletion in the LIS1 gene, whereas the other 20% have a mutation in the XLIS (or DCX) gene located on chromosome Xq22.3-q23. 10,11 Most of the latter patients with X-linked lissencephaly are male and hemizygous for the mutated XLIS gene. Morphological features of the brains of patients with an XLIS mutation resemble those with a LIS1 mutation except for several minor differences.…”

mentioning

confidence: 99%

High Expression of Doublecortin and KIAA0369 Protein in Fetal Brain Suggests Their Specific Role in Neuronal Migration

Mizuguchi

Qin

Yamada

et al. 1999

The American Journal of Pathology

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The X-linked subcortical laminar heterotopia and lissencephaly syndrome is a disorder of neuronal migration caused by a mutation in XLIS, a recently cloned gene on chromosome Xq22.3-q23. The predicted protein product for XLIS, doublecortin (DC), shows high homology to a putative calcium calmodulin-dependent kinase , KIAA0369 protein (KI). Here we identified DC and KI in the brains of human and rat fetuses by immunochemical and immunohistochemical means. In this study , Western blotting demonstrated that both DC and KI are specific to the nervous system and are abundant during the fetal period , around 20 gestational weeks in humans and embryonic days 17 to 20 in rats. Immunostaining of the developing neocortex disclosed localization of DC and KI immunoreactivities in neuronal cell bodies and processes in the zones of ongoing neuronal migration. Although KI showed a somewhat wider distribution than DC , the temporal and spatial patterns of their expression were similar. These results suggest that DC and KI participate in a common signaling pathway regulating neuronal migration. (Am J Pathol 1999, 155:1713-1721)

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Linkage and physical mapping of X-linked lissencephaly/SBH (XLIS): a gene causing neuronal migration defects in human brain

Cited by 90 publications

References 36 publications

Ectopic Doublecortin Gene Expression Suppresses the Malignant Phenotype in Glioblastoma Cells

Ectopic Doublecortin Gene Expression Suppresses the Malignant Phenotype in Glioblastoma Cells

DCX in PC12 cells: CREB-mediated transcription and neurite outgrowth

High Expression of Doublecortin and KIAA0369 Protein in Fetal Brain Suggests Their Specific Role in Neuronal Migration

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