The Testis Determining Factor

What is the TDF?
The TDF is the Testis determining factor, in essence the gene that determines whether an embryo will develop testes or ovaries. The TDF has been found to be the SRY gene (the sex region on the Y chromosome) but this involved a lot of research to get to this point. Firstly they needed to find out where on the Y chromosome the TDF would be located. 

 
Read more about TDF

Where is the TDF?

The X and Y chromosome

A theory first developed was that the TDF would be on the Y chromosome. This was because males had a Y chromosome while females didn't but they wanted to be sure. They found cases of females born with only one X chromosome instead of the usual two and males born with two X chromosomes and one Y chromosome instead of just one X chromosome. It was established from this that the TDF was on the Y chromosome.

Males born with the top part of the Y
chromosome. Showing the placement
of the TDF. *

 Where on the Y chromosome is the TDF?

Studying the Y chromosome in males they found many males who were missing the bottom of the Y chromosome and yet they were still male. From this it could be concluded that the TDF was at the top of the Y chromosome. They also found females who had a Y chromosome but it was missing the top part of the Y chromosome.

Placement of the SRY gene on the Y chromosome

What gene is the TDF?

Placement of the ZFY gene on the Y chromosome
and the absence of it in females with a Y
chromosome. *

Placement of the SRY gene on the Y chromosome and
the absence of it in females with a Y chromosome. *

Now that it was known where the TDF was on the Y chromosome they needed to find out what gene was actually the TDF. A gene was found on the Y chromosome where they thought the TDF would be called the ZDF. It seemed to be the right gene but to be sure they needed to find the ZFY on gene on the Y chromosome on kangaroos to make sure it was the right gene. What they found however was that the ZFY in kangaroos was on the X chromosome meaning that it wasn't the TDF. They then had to start searching again for the correct gene on the Y chromosome that determined sex. After some further research in 1990 the SRY gene was found. It was proved to be the right gene as females who had a Y chromosome but a mutated SRY were female. Further proof that SRY was the right gene was when they cloned the SRY and injected the gene into a mouse XX embryo - a female embryo - the mouse was born male, though it was sterile and had smaller testes.

What does the SRY do?

Not much has been found out about what the SRY gene does but what we do know is that it turns on a gene called SOX9. This gene then sends messages telling the embryo to grow a specific way.

Read more about the SRY

What other genes are involved?

The deletion of DMRT1 in females with a Y chromosome. *

Having an SRY gene and not having an SRY gene does not automatically mean that the embryo is male or female. If the SRY is damaged or mutated then the embryo will grow and embryo. If an embryo has an SRY but there is no DMRT1 gene on the SRY the embryo will be female. Two DMRT1 genes are needed to grow testes. In some cases there are males that do not have an SRY but duplicate SOX9. When there are duplicate SOX9 they manage to turn on themselves. This means that the embryo does not need an SRY to turn on the SOX9 to develop testes.

*Images courtesy of Professor Jenny Graves.