Regulation of left-right patterning in mice by growth/differentiation factor-1

Citation
Ct. Rankin et al., Regulation of left-right patterning in mice by growth/differentiation factor-1, NAT GENET, 24(3), 2000, pp. 262-265
Citations number
22
Categorie Soggetti
Molecular Biology & Genetics
Journal title
NATURE GENETICS
ISSN journal
10614036 → ACNP
Volume
24
Issue
3
Year of publication
2000
Pages
262 - 265
Database
ISI
SICI code
1061-4036(200003)24:3<262:ROLPIM>2.0.ZU;2-#
Abstract
The transforming growth factor-beta (TGF-beta) superfamily encompasses a la rge group of structurally related polypeptides that are capable of regulati ng cell growth and differentiation in a wide range of embryonic and adult t issues(1). Growth/differentiation factor-1 (Gdf-1. encoded by Gdf1) is a TG F-beta family member of unknown function that was originally isolated from an early mouse embryo cDNA library(2) and is expressed specifically in the nervous system in late-stage embryos and adult mice(3). Here we show that a t early stages of mouse development, Gdf1 is expressed initially throughout the embryo proper and then most prominently in the primitive node, ventral neural tube, and intermediate and lateral plate mesoderm. To examine its b iological function, we generated a mouse line carrying a targeted mutation in Gdf1. Gdf1(-/-) mice exhibited a spectrum of defects related to left-rig ht axis formation, including visceral situs inversus, right pulmonary isome rism and a range of cardiac anomalies. In most Gdf1(-/-) embryos, the expre ssion of Ebaf (formerly lefty-1) in the left side of the floor plate and Le ftb (formerly lefty-2), nodal and Pitx2 in the left lateral plate mesoderm was absent, suggesting that Gdf1 acts upstream of these genes either direct ly or indirectly to activate their expression. Our findings suggest that Gd f1 acts early in the pathway of gene activation that leads to the establish ment of left-right asymmetry.