The Role of the Placenta in PWS: Mapping the Expression of PWS Genes

Funding Summary

Dr. Isles and other researchers have shown that abnormal placental function can have profound consequences for brain and behavioral development in the offspring, and that abnormal signaling from the fetal placenta can also have consequences for maternal brain and behavior, which in turn may impact offspring neurodevelopment. This project examines the role of PWS genes in the placenta to understand how they contribute to brain development and behavior. As a first step, the research team will generate a detailed map of PWS gene expression in the placenta, as well as examine the structure and physiology of the placenta in a mouse model of PWS.
Dr. Theresa Strong, Director of Research Programs, shares details on this project in this short video clip.  

Watch the full webinar describing all 9 research projects funded in this grant cycle here

Lay Abstract

Studies of the genes in the Prader-Willi syndrome (PWS) 15q11-q13 interval have focused on their function in the brain. But in fact some of the genes associated with PWS are also strongly expressed in the placenta. Nevertheless, to date there have been no detailed studies of PWS genes in the placenta. This is perhaps understandable given that PWS is a neurodevelopment disorder and most research efforts are focused on understanding what may go awry in the brain. However, work by us and others has shown that abnormal placental function can have profound consequences for brain and behavioral development in the offspring. We now want to examine the role of PWS genes in the placenta and see if they too contribute to brain development and behavior in later life. The placenta, which is mostly derived from the foetus, is actually an incredibly complex organ, with many different cell types contributing to the varied functions the placenta performs. Consequently, to understand what PWS genes are doing, we first need to gain an accurate picture of when and where the PWS genes are expressed in the placenta. To do this we will use newly developed techniques to accurately map PWS gene expression in normal mouse placenta. We will then supplement these data by examining existing placental gene expression datasets derived from normal human samples. We will then begin to examine if the placenta is abnormally structure and/or faulty in a mouse model for PWS. We envisage this project being the first step of a larger overall project that will try and link any changes in placenta function in the mouse model for PWS, with changes in brain and behavior in later life. This programme of work taps into broader questions relating to whether any of the neurodevelopmental phenotypes seen in PWS are, in part, “programmed” by abnormal placental function prior to birth. This may have implications for how we understand the development of the behavioural problems seen in PWS. In turn, this may lead to insights into novel therapeutic interventions and/or treatments.

Funded Year:

2020

Awarded to:

Anthony Isles, Ph.D.

Amount:

$42,972

Institution:

Cardiff University

Researcher:

Anthony Isles, Ph.D.

Search Projects

Donate for PWS Research