Back to the womb

14 January 2018
Presented by Kat Arney.

WOMB.jpg

Baby in womb

This month we’re taking a trip back to the womb - and before - to find out about early development.  Plus, the importance of placentas, why the age of your womb - rather than your eggs - matters, and a video game-inspired gene of the month.

In this episode

01:04 - Special stem cells

Life, the universe and pluripotent stem cells

Special stem cells
with Peter Rugg-Gunn, Babraham Institute

This month on Naked Genetics we  journey back in time to the earliest moments in life as a foetus grows in the womb. Our story starts at the moment of fertilisation, when egg and sperm meet, creating a fertilised egg or zygote...

This single cell, somehow containing all the information needed to make a baby, divides to form an embryo, made up of special stem cells. In turn, these stem cells divide and specialise, eventually making all the tissues of the body. So how does that work?

In search of these hidden biological secrets Kat Arney went on a journey of her own - up the M11 to the Babraham Institute just outside Cambridge - to meet some of the UK’s leading developmental biologists.

Peter Rugg-Gunn, group leader at the Babraham Institute is fascinated by so-called pluripotent stem cells - cells that can turn into all kinds of different tissues. Kat wanted to know why exactly are they so interesting?

Female body builder

11:34 - Building muscle

Researchers have grown functioning human muscle from reprogrammed stem cells

Building muscle

Induced pluripotent stem cells - or iPS cells for short - are one of the hottest topics in biology right now, and have the potential to transform medicine...

This month, researchers led by Nenad Bursac at Duke University in the US have announced that they’ve managed to grow the first functioning human skeletal muscle from iPS cells, providing an exciting path towards new treatments for muscle wasting diseases.

Publishing in the journal Nature Communications, the scientists are building on their previous work growing functional muscle tissue from stem cells extracted from small samples of fully-grown muscle tissue, transplanting the cells onto a supportive three-dimensional scaffold that allowed them to grow into fully-formed muscle fibres. But the number of these stem cells is limited, and can only be obtained by taking an invasive muscle biopsy.

This time the team started with iPS cells, which can be made from cells obtained less invasively such as skin or blood, and turned them into muscle stem cells with the help of a protein known as Pax7 - a key transcription factor involved in muscle development.

Impressively, the lab-grown muscle fibres could contract and respond to electrical or chemical signals - just like real muscles in the body. And when they were transplanted into mice, the lab grown muscles soon settled down and started to grow a blood supply, surviving for at least three weeks.

There’s still a lot more work to be done to build up this body-building technology - the lab-grown muscles from iPS cells aren’t as strong as ones grown from muscle-derived stem cells, but the scientists are still hopeful that the technique could be used to develop and test treatments for rare but devastating muscle-wasting diseases and maybe one day even provide new muscle tissue for transplantation.

A human egg cell

13:42 - Inside the egg

Strange things are going on inside egg cells

Inside the egg
with Courtney Hanna - Babraham Institute

Now it’s time to wind the developmental clock back even further -all the way back to the egg. Courtney Hanna, a postdoc at the Babraham Institute, is investigating the curious characteristics of mammalian egg cells and the special cells, known as oocytes, that they come from...

She’s using mice as a model and focusing particularly on DNA methylation - an epigenetic mark found around the control switches, or regulatory regions, on DNA that tells cells important information about whether certain genes are active or not, forming a kind of programme for how cells should behave.

As Courtney explained to Kat Arney, taking a closer look at the changes, or reprogramming, of these epigenetic marks as oocytes change into eggs and are then fertilised she’s hoping to understand the events that happen at the very earliest moments of life.

Drawing of a placenta

22:27 - In praise of the placenta

Don't throw that placenta in the bin - study it!

In praise of the placenta
with Myriam Hemberger, Babraham Institute

The stem cells in an early embryo decide whether they’re going to form the embryo itself, or play a supporting role in the placenta and other extra-embryonic tissues. Most developmental biologists focus on the embryo as it grows into a foetus - after all, that’s what becomes a baby once it’s born, so that’s super-interesting - right?

But most cases of pregnancy loss and pre-term birth are caused by problems with the placenta rather than the developing fetus. Yet, as Kat Arney discovered when she talked to Myriam Hemberger at the Babraham Institute, this vital organ has been tragically ignored.

Link from Legend of Zelda

32:17 - Gene of the Month - Zelda

A master controller inspired by a computer game.

Gene of the Month - Zelda

Found in fruit flies - aren’t they all? - Zelda wasn’t actually this gene’s first name. It was originally known as Vielfaeltig, a German word meaning versatile or diverse, coined by researchers in the German lab where it was first discovered in 2006...

They discovered that a faulty version of the gene affected cell division in fly embryos, leading to many different problems ranging from issues with segmentation and muscle development to abnormalities in the nervous system, suggesting that the product of the gene was highly versatile and played many roles in fly development - hence the name.

But in 2008, a team led by Christine Rushlow in New York published a paper in the journal Nature, showing exactly what the protein encoded by the gene did. They named the protein Zinc-finger early Drosophila activator, abbreviated to ZELDA, reflecting its role in switching on many genes early on in fruit fly development.

Because the name Zelda was snappier and easier to pronounce, and better reflected the actual structure and function of the product, it stuck. Oh, and the fact that a PhD student who worked on the study was a huge fan of the video game Princess of Zelda might have had something to do with it too…

We now know Zelda is a master regulator transcription factor, involved in switching on a huge range of genes in the fertilised egg at the very earliest stages of a fruit fly’s life, playing a major role in shaping the form and function of the insect as it grows and develops.

It works antagonistically with another transcription factor called Grainyhead, with both proteins able to stick to the same sequence of DNA - CAGGTAG, if you’re interested - which is found near the start of many crucial developmental genes, and Zelda seems to hold open the DNA so genes can be switched on.

Find out more about Zelda: http://www.michaeleisen.org/blog/?p=617

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