Cueing up at the meiotic starting line

December 11, 2008

CAMBRIDGE, Mass. (Dec. 12, 2008) -- Meiosis, the process of halving a germ cell's chromosomes in preparation for egg or sperm production, has been one of the most studied areas of cell biology. But in mammals, the field has been divided over the question of whether meiosis is triggered by a signal within a cell or by a signal coming from the cell's environment.

Now new research from the lab of Whitehead Director David Page reveals that both sets of signals are needed to initiate meiosis.

In 2006,the Page lab showed that an external signal of retinoic acid (RA), a derivative of vitamin A, starts the expression of the Stra8 gene, which is seen at the very beginning of meiosis. While this research seemed to settle the controversy, researchers still had to deal with the reality that RA has signaling functions throughout the body at various points of development. How could such a nonspecific signal have such a specific effect on meiosis in embryonic germ cells? As it turns out, other researchers in Page's lab were grappling with that very issue.

Coincidentally, more than 10 years before the work on RA, Page's lab had been studying the effects of a few genes on human male fertility, noting at the time that one such gene, known as Dazl, codes for a germ cell-specific protein that binds to RNA. But at the time, no one knew that the Dazl gene is an integral part of the RA signaling pathway in embryonic germ cells.

"Dazl is in both the mouse and human genomes, but it has counterparts that are critical in germ cell biology throughout the entire animal kingdom," says Page.

To see how the Dazl gene affects germ cells' response to RA signaling, Page graduate students Yanfeng Lin and Mark Gill compared the embryonic ovaries of control mice to those of mice lacking the DAZL protein. They stained the ovaries for Stra8 expression, a clear indicator of meiotic initiation. The ovaries without the DAZL protein failed to express Stra8 and thus did not enter meiosis. Control mice, however, which had the DAZL protein, clearly expressed Stra8 and became meiotic.

Gill explains that the Dazl gene and its protein prepare the cell to respond to RA. "We've uncovered a transition state in development in which the cells are primed for meiosis," says Gill. "This research further explains the specificity of the retinoic acid signaling pathway that had been previously described."

Although part of the meiosis initiation mystery has been elucidated, Page concedes this is only the beginning. "There's a lot of black box here, like what is going on in the cell during this transitional state. We're addressing that as well, which is why this is a very exciting time in this field."
-end-
David Page's primary affiliation is with Whitehead Institute for Biomedical Research, where his laboratory is located and all his research is conducted. He is also a Howard Hughes Medical Institute investigator and a professor of biology at Massachusetts Institute of Technology.



Full citation:

Science, 322 (5908):1685-1687, December 12, 2008.

Yanfeng Lin (1,2), Mark E. Gill (1,2), Jana Koubova (1) and David C. Page (1)

1. Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA
2. These authors contributed equally to this work.

Whitehead Institute for Biomedical Research

Related Cell Biology Articles from Brightsurf:

Deep learning on cell signaling networks establishes AI for single-cell biology
Researchers at CeMM have developed knowledge-primed neural networks (KPNNs), a new method that combines the power of deep learning with the interpretability of biological network models.

RNA biology provides the key to cell identity and health
Two papers in Genome Research by the FANTOM Consortium have provided new insights into the core regulatory networks governing cell types in different vertebrate species, and the role of RNA as regulators of cell function and identity.

Cell biology: Your number's up!
mRNAs program the synthesis of proteins in cells, and their functional lifetimes are dynamically regulated.

Cell biology -- maintaining mitochondrial resilience
Mitochondria cannot autonomously cope with stress and must instead call on the cell for help.

Cell biology: All in a flash!
Scientists of Ludwig-Maximilians-Universitaet (LMU) in Munich have developed a tool to eliminate essential proteins from cells with a flash of light.

A biology boost
Assistance during the first years of a biology major leads to higher retention of first-generation students.

Cell-free synthetic biology comes of age
In a review paper published in Nature Reviews Genetics, Professor Michael Jewett explores how cell-free gene expression stands to help the field of synthetic biology dramatically impact society, from the environment to medicine to education.

Scientists develop electrochemical platform for cell-free synthetic biology
Scientists at the University of Toronto (U of T) and Arizona State University (ASU) have developed the first direct gene circuit to electrode interface by combining cell-free synthetic biology with state-of-the-art nanostructured electrodes.

In a first for cell biology, scientists observe ribosome assembly in real time
A team of scientists from Scripps Research and Stanford University has recorded in real time a key step in the assembly of ribosomes -- the complex and evolutionarily ancient 'molecular machines' that make proteins in cells and are essential for all life forms.

Cell biology: Endocannabinoid system may be involved in human testis physiology
The endocannabinoid system (ECS) may be directly involved in the regulation of the physiology of the human testis, including the development of sperm cells, according to a study in tissue samples from 15 patients published in Scientific Reports.

Read More: Cell Biology News and Cell Biology Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.