Features | Partner Sites | Information | LinkXpress
Sign In
GLOBETECH PUBLISHING LLC
GLOBETECH PUBLISHING LLC
GLOBETECH MEDIA

A Transcription Factor Feedback Loop Controls Early Placenta Development

By BiotechDaily International staff writers
Posted on 30 Apr 2013
The molecular pathways leading to development of the placenta are regulated by a feedback loop between the transcription factors Gcm1 (chorion-specific transcription factor or hGCMa), which is a mammalian homologue of the Drosophila GCM (glia cells missing) and Fzd5 (Frizzled5).

Abnormal placental development during pregnancy is associated with conditions such as preeclampsia, intrauterine growth restriction, and even fetal death in humans. Investigators at the Chinese Academy of Sciences (Beijing) worked with a mouse model of placental development that closely mimicked the process in humans. They focused on the earliest steps of placenta formation, which involves the development of the labyrinthine layer, a specialized epithelium that sits between the maternal blood and fetal blood vessels and facilitates the exchange of nutrients, gases, and wastes between the mother and fetus. Pivotal to the development of a functional labyrinth layer are the processes of folding and branching of a flat sheet of trophoblast cells (originally the outer layer of the blastocyst), and of trophoblast cell differentiation.

Results published in the April 16, 2013, online edition of the journal PLOS Biology revealed that in mice Fzd5, a receptor component of the Wnt signaling pathway, and Gcm1, an important transcription factor for labyrinth development, formed a positive feedback loop that directed normal placental development. Gcm1 up-regulated Fzd5 specifically at branching sites, and elevated Fzd5 expression in turn maintained expression of Gcm1.

Fzd5-mediated signaling was required for the disassociation of cell junctions and for the up-regulation of VEGF (vascular endothelial growth factor) expression in trophoblast cells. Furthermore, the FZD5-GCM1 signaling cascade was found to operate in primary cultures of human trophoblasts undergoing differentiation.

"We provide here genetic, molecular, pharmacological, and physiological evidence that an amplifying feedback loop between Gcm1 and Fzd5 is essential for normal placental development of mice," said senior author Dr. Haibin Wang, professor of developmental biology at the Chinese Academy of Sciences. "Besides shedding light on the fundamental mechanisms of branching morphogenesis during mouse placental development, the finding has high clinical relevance, since the Gcm1-Fzd5 signaling cascade also operates in human trophoblasts, and when its regulation goes wrong, it can be linked to trophoblast-related diseases, such as preeclampsia."

Related Links:
Chinese Academy of Sciences


Channels

Drug Discovery

view channel
Image: Star-like glial cells in red surround alpha-beta plaques in the cortex of a mouse with a model of Alzheimer\'s disease (Photo courtesy of Strittmatter laboratory/Yale University).

Experimental Cancer Drug Reverses Symptoms in Mouse Model of Alzheimer's Disease

An experimental, but clinically disappointing drug for treatment of cancer has been found to be extremely effective in reversing the symptoms of Alzheimer's disease (AD) in a mouse model.... Read more

Biochemistry

view channel
Image:  Model depiction of a novel cellular mechanism by which regulation of cryptochromes Cry1 and Cry2 enables coordination of a protective transcriptional response to DNA damage caused by genotoxic stress (Photo courtesy of the journal eLife, March 2015, Papp SJ, Huber AL, et al.).

Two Proteins Critical for Circadian Cycles Protect Cells from Mutations

Scientists have discovered that two proteins critical for maintaining healthy day-night cycles also have an unexpected role in DNA repair and protecting cells against genetic mutations that could lead... Read more

Business

view channel

NanoString and MD Anderson Collaborate on Development of Novel Multi-Omic Expression Profiling Assays for Cancer

The University of Texas MD Anderson Cancer Center (Houston, TX, USA) and NanoString Technologies, Inc. (Seattle, WA, USA) will partner on development of a revolutionary new type of assay—simultaneously profiling gene and protein expression, initially aiming to discover and validate biomarker signatures for immuno-oncology... Read more
 

Events

21 Apr 2015 - 23 Apr 2015
21 Apr 2015 - 23 Apr 2015
Copyright © 2000-2015 Globetech Media. All rights reserved.