Study shows gene's role in developing and maintaining cells key for a lifetime of memories

Aug 18, 2010

St. Jude Children's Research Hospital investigators showed a gene named Prox1 is a key player in normal development of a brain structure crucial for learning and memory and remains active throughout life, nurturing the cells vital for making new memories.

This study focused on a small region of the known as the dentate gyrus, a needed for memory and learning that is home to the subgranular zone where the neural stem cells destined to become granule cells are housed. The dentate gyrus is one of two regions of the adult brain where neural stem cells continue to produce the that ultimately differentiate into .

Although investigators knew Prox1 was expressed during development of the dentate gyrus, this is the first report detailing the gene's function in this region of the brain. Prox1 is a transcription factor that functions like an on-off switch for genes.

Researchers showed that by removing Prox1 at different stages of mouse development, the dentate gyrus fails to develop properly. Investigators also demonstrated that Prox1 remains important throughout mammalian life to ensure production of new granule cells, which are needed to form new memories. The work appears in the August 17 edition of PloS Biology.

The findings raise the possibility that subtle mutations in Prox1 might be linked to memory and learning problems, said the paper's senior author Guillermo Oliver, Ph.D., member of the St. Jude Department of Genetics. "The more we understand about how signaling pathways work in the brain, the more we will eventually be able to manipulate the system to promote or block the differentiation process," he said.

Although this is the first detailed report of the role Prox1 plays in normal brain development, earlier studies suggest the gene is central to normal development in a wide range of organs and cell types. Prox1 also plays a role in several types of cancers.

In this study, investigators determined that in the adult mammalian , Prox1 is active during a particular stage of differentiation when neural stem cells change from cells of unlimited potential to more specialized granule cells. The scientists reported that in the dentate gyrus Prox1 is produced by intermediate progenitor cells and that the lack of Prox1 results in death of these intermediate cells. Without these intermediate progenitor cells, new adult granule cells do not develop.

Researchers also linked Prox1 to a feedback mechanism that signals stem cells to stop differentiating. "When we switched off the expression of the Prox1 gene in mice and the intermediate progenitor cells disappeared, the adult neural stem cells continued differentiating into granule cells until the supply of stem cells was exhausted. When we switched on Prox1 in these adult neural stem cells, we observed a similar depletion of stem cells caused by their premature differentiation," Oliver said. Investigators are still studying the signaling pathways involved.

The paper's first author, Alfonso Lavado, Ph.D., a postdoctoral fellow in Oliver's laboratory, added: "It was surprising to find out that the loss of Prox1 in intermediate progenitors impacted neural stem cells. Without the intermediate progenitors, their mother cells, the , also disappear. That shows the progeny is somehow needed to maintain the mother cells when new neuronal cells develop."

These findings indicate that during dentate gyrus development and adult neurogenesis, Prox1 is necessary for the differentiation of granule cells and reveals a regulatory mechanism that links the production of the proper number of new granule cells to the maintenance of adult stem cells.

Explore further: First genetic link discovered to difficult-to-diagnose breast cancer sub-type

Provided by St. Jude Children's Research Hospital

not rated yet
add to favorites email to friend print save as pdf

Related Stories

When is a stem cell not really a stem cell?

Aug 26, 2007

Working with embryonic mouse brains, a team of Johns Hopkins scientists seems to have discovered an almost-too-easy way to distinguish between “true” neural stem cells and similar, but less potent versions. Their finding, ...

New study hopeful on neural stem cells

Aug 05, 2006

Neural stem cells derived from federally approved human embryonic cells are inferior to stem cells derived from donated fetal tissue, a new study found.

A genetic basis for schizophrenia

Jul 21, 2009

Schizophrenia is a severely debilitating psychiatric disease that is thought to have its roots in the development of the nervous system; however, major breakthroughs linking its genetics to diagnosis, prognosis and treatment ...

Recommended for you

Refining the language for chromosomes

Apr 17, 2014

When talking about genetic abnormalities at the DNA level that occur when chromosomes swap, delete or add parts, there is an evolving communication gap both in the science and medical worlds, leading to inconsistencies in ...

Down's chromosome cause genome-wide disruption

Apr 16, 2014

The extra copy of Chromosome 21 that causes Down's syndrome throws a spanner into the workings of all the other chromosomes as well, said a study published Wednesday that surprised its authors.

User comments : 0

More news stories

Filipino tests negative for Middle East virus

A Filipino nurse who tested positive for the Middle East virus has been found free of infection in a subsequent examination after he returned home, Philippine health officials said Saturday.

Study says we're over the hill at 24

(Medical Xpress)—It's a hard pill to swallow, but if you're over 24 years of age you've already reached your peak in terms of your cognitive motor performance, according to a new Simon Fraser University study.

NASA's space station Robonaut finally getting legs

Robonaut, the first out-of-this-world humanoid, is finally getting its space legs. For three years, Robonaut has had to manage from the waist up. This new pair of legs means the experimental robot—now stuck ...

Ex-Apple chief plans mobile phone for India

Former Apple chief executive John Sculley, whose marketing skills helped bring the personal computer to desktops worldwide, says he plans to launch a mobile phone in India to exploit its still largely untapped ...

Egypt archaeologists find ancient writer's tomb

Egypt's minister of antiquities says a team of Spanish archaeologists has discovered two tombs in the southern part of the country, one of them belonging to a writer and containing a trove of artifacts including reed pens ...

Airbnb rental site raises $450 mn

Online lodging listings website Airbnb inked a $450 million funding deal with investors led by TPG, a source close to the matter said Friday.