Not so fast: Differences in the first embryonic cell lineage decision of mammals

Feb 14, 2011

New research shows that all not mammals are created equal. In fact, this work shows that the animals most commonly used by scientists to study mammalian genetics -- mice -- develop unusually quickly and may not always be representative of embryonic development in other mammals. The study, published by Cell Press in the February 14 issue of the journal Developmental Cell, identifies significant differences in the timing of cell fate commitment during mouse and cattle embryonic development and raises important strategic implications for the generation of embryonic stem cells.

The in mammals is formed from cells called trophectoderm that arise from the very first lineage decision made by the early embryo. Most trophectoderm research is performed on mice, as other mammals tend to be much harder to work with in a lab. In the mouse, the fate of trophoectoderm cells is sealed (committed) by the mid-blastocyst stage. This fate commitment is driven in part by repression of the stem cell factor Oct4.

"We were intrigued by previous observations that in mammals such as humans, cattle, pigs and rabbits Oct4 protein was not shut down in the trophoectoderm of late blastocyst embryos," explains senior author Dr. Peter L. Pfeffer from AgResearch Crown Research Institute in Hamilton, New Zealand. Using cattle as a non-rodent model system, Dr. Pfeffer and colleagues discovered that cattle trophoectoderm cells were committed to their fate much later than mouse cells, with Oct4 expression levels remaining strong for longer than in mice. In fact the authors identified the specific evolutionary changes in mouse DNA that make Oct4 behave differently in mice than in other mammals.

"Somewhat ironically, our studies in cattle led to new insight into Oct4 regulation in the mouse," explains Dr Pfeffer. "Such evolutionary differences in the regulation of the key stem cell gene Oct4 may explain the difficulty in embryonic stem cell derivation in mammals other than the mouse." Based on the fact that mouse implant in the uterus at an earlier developmental stage than other mammals do, and therefore require earlier trophectoderm formation, the authors also speculate that the unusually rapid repression of Oct4 in mouse trophectoderm represented a key evolutionary step enabling early implantation.

"Establishing cattle as a second functional mammalian embryological model system challenges notions that mice are representative of either the earliest stages of mammalian development or of embryonic stem cell biology," concludes Dr. Pfeffer.

Explore further: Molecular gate that could keep cancer cells locked up

add to favorites email to friend print save as pdf

Related Stories

Adult stem cells lack key pluripotency regulator

Oct 10, 2007

The protein Oct4 plays a major role in embryonic stem cells, acting as a master regulator of the genes that keep the cells in an undifferentiated state. Unsurprisingly, researchers studying adult stem cells have long suspected ...

Ronin an alternate control for embryonic stem cells

Jun 26, 2008

Like the masterless samurai for whom it is named, the protein Ronin chooses an independent path, maintaining embryonic stem cells in their undifferentiated state and playing essential roles in genesis of embryos and their ...

Team IDs mechanism for multiplying adult stem cells

May 25, 2005

While research on human embryonic stem cells gets most of the press, scientists are also investigating the potential therapeutic uses of adult stem cells. Although less controversial, this research faces other difficulties. ...

Recommended for you

Molecular gate that could keep cancer cells locked up

17 hours ago

In a study published today in Genes & Development, Dr Christian Speck from the MRC Clinical Sciences Centre's DNA Replication group, in collaboration with Brookhaven National Laboratory (BNL), New York, ...

The 'memory' of starvation is in your genes

20 hours ago

During the winter of 1944, the Nazis blocked food supplies to the western Netherlands, creating a period of widespread famine and devastation. The impact of starvation on expectant mothers produced one of the first known ...

Sugar mimics guide stem cells toward neural fate

Jul 30, 2014

Embryonic stem cells can develop into a multitude of cells types. Researchers would like to understand how to channel that development into the specific types of mature cells that make up the organs and other structures of ...

User comments : 0