Ott1 (Rbm15) is essential for placental vascular branching morphogenesis and embryonic development of the heart and spleen.

Authors

G D. Raffel
G C. Chu
J L. Jesneck
D E. Cullen
R T. Bronson
O A. Bernard
D G. Gilliland

Document Type

Article

Publication Date

2009

Keywords

Cell-Hypoxia, Drosophila-Proteins, Embryo-Mammalian, Female, Gene-Deletion, Gene-Expression-Regulation-Developmental, Heart, In-Situ-Hybridization, Mice-Knockout, Mice-Transgenic, Morphogenesis, Organogenesis, Placenta, Pregnancy, RNA-Binding-Proteins, Spleen, Trophoblasts, Vascular-Endothelial-Growth-Factors

First Page

333

Last Page

341

JAX Source

Mol Cell Biol 2009 Jan; 29(2):333-41.

Abstract

The infant leukemia-associated gene Ott1 (Rbm15) has broad regulatory effects within murine hematopoiesis. However, germ line Ott1 deletion results in fetal demise prior to embryonic day 10.5, indicating additional developmental requirements for Ott1. The spen gene family, to which Ott1 belongs, has a transcriptional activation/repression domain and RNA recognition motifs and has a significant role in the development of the head and thorax in Drosophila melanogaster. Early Ott1-deficient embryos show growth retardation and incomplete closure of the notochord. Further analysis demonstrated placental defects in the spongiotrophoblast and syncytiotrophoblast layers, resulting in an arrest of vascular branching morphogenesis. The rescue of the placental defect using a conditional allele with a trophoblast-sparing cre transgene allowed embryos to form a normal placenta and survive gestation. This outcome showed that the process of vascular branching morphogenesis in Ott1-deficient animals was regulated by the trophoblast compartment rather than the fetal vasculature. Mice surviving to term manifested hyposplenia and abnormal cardiac development. Analysis of global gene expression of Ott1-deficient embryonic hearts showed an enrichment of hypoxia-related genes and a significant alteration of several candidate genes critical for cardiac development. Thus, Ott1-dependent pathways, in addition to being implicated in leukemogenesis, may also be important for the pathogenesis of placental insufficiency and cardiac malformations.

Recommended Citation

Raffel GD, Chu GC, Jesneck JL, Cullen DE, Bronson RT, Bernard OA, Gilliland DG. Ott1 (Rbm15) is essential for placental vascular branching morphogenesis and embryonic development of the heart and spleen. Mol Cell Biol 2009 Jan; 29(2):333-41.