TBX5 transcription factor regulates cell proliferation during cardiogenesis

Authors

Cathy J. Hatcher, Philadelphia College of Osteopathic MedicineFollow
Minsu Kim
Caroline S. Maha
Marsha M. Goldstein
Benjamin Wong
Takashi Mikawa
Craig T. Basson

Document Type

Article

Publication Date

2001

Abstract

Mutations in human TBX5, a member of the T-box transcription factor gene family, cause congenital cardiac septation, defects and isomerism in autosomal dominant Holt-Oram syndrome. To determine the cellular function of TBX5 in cardiogenesis, we overexpressed wild-type and mutant human TBX5 isoforms in vitro and in vivo. TBX5 inhibited cell proliferation of D17 canine osteosarcoma cells and MEQC quail cardiomyocyte-like cells in vitro. Mutagenesis of the 5′ end of the T-box but not the 3′ end of the T-box abolished this effect. Overexpression of TBX5 in embryonic chick hearts showed that TBX5 inhibits myocardial growth and trabeculation. TBX5 effects in vivo were abolished by Gly80Arg missense mutation of the 5′ end of the T-box. PCNA analysis in transgenic chick hearts revealed that TBX5 overexpression does suppress embryonic cardiomyocyte proliferation in vivo. Inhibitory effects of TBX5 on cardiomyocyte proliferation include a noncell autonomous process in vitro and in vivo. TBX5 inhibited proliferation of both nontransgenic cells cocultured with transgenic cells in vitro and nontransgenic cardiomyocytes in transgenic chick hearts with mosaic expression of TBX5 in vivo. Immunohistochemical studies of human embryonic tissues, including hearts, also demonstrated that TBX5 expression is inversely related to cellular proliferation. We propose that TBX5 can act as a cellular arrest signal during vertebrate cardiogenesis and thereby participate in modulation of cardiac growth and development. © 2001 Academic Press.

Publication Title

Developmental biology

Volume

230

Issue

2

First Page

177

Last Page

188

Comments

This article was published in Developmental biology, Volume 230, Issue 2, Pages 177-188.

The published version is available at http://dx.doi.org/10.1006/dbio.2000.0134.

Copyright © 2001 Elsevier and available under license.

Recommended Citation

Hatcher, Cathy J.; Kim, Minsu; Maha, Caroline S.; Goldstein, Marsha M.; Wong, Benjamin; Mikawa, Takashi; and Basson, Craig T., "TBX5 transcription factor regulates cell proliferation during cardiogenesis" (2001). PCOM Scholarly Papers. 516.
https://digitalcommons.pcom.edu/scholarly_papers/516