Features | Partner Sites | Information | LinkXpress
Sign In
JIB
GLOBETECH PUBLISHING
GLOBETECH PUBLISHING

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


comments powered by Disqus

Channels

Drug Discovery

view channel
Image: Synthetic ion transporters can induce apoptosis by facilitating chloride anion transport into cells (Photo courtesy of the University of Texas, Austin).

Experimental Drug Kills Cancer Cells by Interfering with Their Ion Transport Mechanism

An experimental anticancer drug induces cells to enter a molecular pathway leading to apoptosis by skewing their ion transport systems to greatly favor the influx of chloride anions. To promote development... Read more

Therapeutics

view channel
Image: Liver cells regenerated in mice treated with a new drug (right) compared with a control group (center) after partial liver removal. Healthy liver cells are shown at left (Photo courtesy of Marshall et al, 2014, the Journal of Experimental Medicine).

New Drug Triggers Liver Regeneration After Surgery

Investigators have revealed that an innovative complement inhibitor decreases complement-mediated liver cell death, and actually stimulates postsurgery liver regrowth in mice. Liver cancer often results... Read more

Lab Technologies

view channel

White-Matter Deficits Found in Codeine-Containing Cough Syrup Users

A magnetic resonance imaging (MRI) study of chronic users of codeine-containing cough syrups (CCS) has found deficits in specific regions of brain white matter and linked these changes with increased impulsivity in codeine-containing cough syrup users. These findings were consistent with findings from earlier research of... Read more

Business

view channel

Partnership Established to Decode Bowel Disease

23andMe (Mountain View, CA,USA), a personal genetics company, is collaborating with Pfizer, Inc. (New York, NY, USA), in which the companies will seek to enroll 10,000 people with inflammatory bowel disease (IBD) in a research project designed to explore the genetic factors associated with the onset, progression, severity,... Read more
 
Copyright © 2000-2014 Globetech Media. All rights reserved.