UMMS Affiliation

Department of Neurobiology; Budnik Lab

Publication Date

2010-09-15

Document Type

Article

Subjects

Animals; Cell Nucleus; Drosophila melanogaster; Ecdysone; *Gene Expression Regulation, Developmental; Lamin Type A; Muscles; Signal Transduction

Disciplines

Neuroscience and Neurobiology

Abstract

The inner side of the nuclear envelope (NE) is lined with lamins, a meshwork of intermediate filaments that provides structural support for the nucleus and plays roles in many nuclear processes. Lamins, classified as A- or B-types on the basis of biochemical properties, have a conserved globular head, central rod and C-terminal domain that includes an Ig-fold structural motif. In humans, mutations in A-type lamins give rise to diseases that exhibit tissue-specific defects, such as Emery-Dreifuss muscular dystrophy. Drosophila is being used as a model to determine tissue-specific functions of A-type lamins in development, with implications for understanding human disease mechanisms. The GAL4-UAS system was used to express wild-type and mutant forms of Lamin C (the presumed Drosophila A-type lamin), in an otherwise wild-type background. Larval muscle-specific expression of wild type Drosophila Lamin C caused no overt phenotype. By contrast, larval muscle-specific expression of a truncated form of Lamin C lacking the N-terminal head (Lamin C DeltaN) caused muscle defects and semi-lethality, with adult 'escapers' possessing malformed legs. The leg defects were due to a lack of larval muscle function and alterations in hormone-regulated gene expression. The consequences of Lamin C association at a gene were tested directly by targeting a Lamin C DNA-binding domain fusion protein upstream of a reporter gene. Association of Lamin C correlated with localization of the reporter gene at the nuclear periphery and gene repression. These data demonstrate connections among the Drosophila A-type lamin, hormone-induced gene expression and muscle function.

Rights and Permissions

© 2010. Published by The Company of Biologists Ltd. Publisher PDF posted as allowed by the publisher's author rights policy at http://dev.biologists.org/site/misc/rights_permissions.xhtml#author.

DOI of Published Version

10.1242/dev.048231

Source

Development. 2010 Sep;137(18):3067-77. Epub 2010 Aug 11. Link to article on publisher's site

Journal/Book/Conference Title

Development (Cambridge, England)

Related Resources

Link to Article in PubMed

PubMed ID

20702563

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