ATXN1 Protein Family and CIC Regulate Extracellular Matrix Remodeling and Lung Alveolarization

44Citations
Citations of this article
55Readers
Mendeley users who have this article in their library.

Abstract

Although expansion of CAG repeats in ATAXIN1 (ATXN1) causes Spinocerebellar ataxia type 1, the functions of ATXN1 and ATAXIN1-Like (ATXN1L) remain poorly understood. To investigate the function of these proteins, we generated and characterized Atxn1L -/- and Atxn1 -/-; Atxn1L -/- mice. Atxn1L -/- mice have hydrocephalus, omphalocele, and lung alveolarization defects. These phenotypes are more penetrant and severe in Atxn1 -/-; Atxn1L -/- mice, suggesting that ATXN1 and ATXN1L are functionally redundant. Upon pursuing the molecular mechanism, we discovered that several Matrix metalloproteinase (Mmp) genes are overexpressed and that the transcriptional repressor Capicua (CIC) is destabilized in Atxn1L -/- lungs. Consistent with this, Cic deficiency causes lung alveolarization defect. Loss of either ATXN1L or CIC derepresses Etv4, an activator for Mmp genes, thereby mediating MMP9 overexpression. These findings demonstrate a critical role of ATXN1/ATXN1L-CIC complexes in extracellular matrix (ECM) remodeling during development and their potential roles in pathogenesis of disorders affecting ECM remodeling. © 2011 Elsevier Inc.

Cite

CITATION STYLE

APA

Lee, Y., Fryer, J. D., Kang, H., Crespo-Barreto, J., Bowman, A. B., Gao, Y., … Zoghbi, H. Y. (2011). ATXN1 Protein Family and CIC Regulate Extracellular Matrix Remodeling and Lung Alveolarization. Developmental Cell, 21(4), 746–757. https://doi.org/10.1016/j.devcel.2011.08.017

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free