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Citation
Wu, Y., Gause, M., Xu, D., Misulovin, Z., Schaaf, C.A., Mosarla, R.C., Mannino, E., Shannon, M., Jones, E., Shi, M., Chen, W.F., Katz, O.L., Sehgal, A., Jongens, T.A., Krantz, I.D., Dorsett, D. (2015). Drosophila Nipped-B Mutants Model Cornelia de Lange Syndrome in Growth and Behavior.  PLoS Genet. 11(11): e1005655.
FlyBase ID
FBrf0230079
Publication Type
Research paper
Abstract

Individuals with Cornelia de Lange Syndrome (CdLS) display diverse developmental deficits, including slow growth, multiple limb and organ abnormalities, and intellectual disabilities. Severely-affected individuals most often have dominant loss-of-function mutations in the Nipped-B-Like (NIPBL) gene, and milder cases often have missense or in-frame deletion mutations in genes encoding subunits of the cohesin complex. Cohesin mediates sister chromatid cohesion to facilitate accurate chromosome segregation, and NIPBL is required for cohesin to bind to chromosomes. Individuals with CdLS, however, do not display overt cohesion or segregation defects. Rather, studies in human cells and model organisms indicate that modest decreases in NIPBL and cohesin activity alter the transcription of many genes that regulate growth and development. Sister chromatid cohesion factors, including the Nipped-B ortholog of NIPBL, are also critical for gene expression and development in Drosophila melanogaster. Here we describe how a modest reduction in Nipped-B activity alters growth and neurological function in Drosophila. These studies reveal that Nipped-B heterozygous mutant Drosophila show reduced growth, learning, and memory, and altered circadian rhythms. Importantly, the growth deficits are not caused by changes in systemic growth controls, but reductions in cell number and size attributable in part to reduced expression of myc (diminutive) and other growth control genes. The learning, memory and circadian deficits are accompanied by morphological abnormalities in brain structure. These studies confirm that Drosophila Nipped-B mutants provide a useful model for understanding CdLS, and provide new insights into the origins of birth defects.

PubMed ID
PubMed Central ID
PMC4636142 (PMC) (EuropePMC)
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Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    PLoS Genet.
    Title
    PLoS Genetics
    Publication Year
    2005-
    ISBN/ISSN
    1553-7404 1553-7390
    Data From Reference
    Alleles (8)
    Genes (3)
    Human Disease Models (1)
    Transgenic Constructs (3)