Gene's Role in Making and Keeping Memories

Researchers from St. Jude Children’s Research Hospital, whose study results were published online August 17 in PLoS Biology, have determined the role played by the homeobox gene Prox1in the dentate gyrus region of the hippocampus, a structure highly involved in memory, learning, embryonic development, and neurogenesis.With knowledge that the dentate gyrus is home to the subgranular zone—which houses neural stem cells that will become granule cells—and that the dentate gyrus is one of two brain regions where neural stem cells produce precursor cells that become neurons in adult brains, the research team sought to determine the exact function of Prox1in the dentate gyrus.

Led by Guillermo Oliver, PhD, Department of Genetics, the team found that “Prox1is necessary for the maturation of granule cells in the dentate gyrus during development and for the maintenance of intermediate progenitors during adult neurogenesis.” Additionally, they demonstrated that “Prox1-expressing intermediate progenitors are required for adult neural stem cell self-maintenance in the subgranular zone; thus, we have identified a previously unknown non-cell autonomous regulatory feedback mechanism that controls adult neurogenesis in this region of the mammalian brain. Finally, [they] show that the ectopic expression of Prox1 induces premature differentiation of neural stem cells.”

According to Oliver, the findings show that subtle mutations in Prox1might be linked with memory and learning problems. "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 added.

In the study, Prox1was also linked to a feedback mechanisms that halt the differentiating of stem cells. “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” said Oliver. “When we switched on Prox1 in these adult neural stem cells, we observed a similar depletion of stem cells caused by their premature differentiation."

Lead author on the study, Alfonso Lavado, PhD, postdoctoral fellow in Oliver’s laboratory added that 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 neural stem cells, also disappear. That shows the progeny is somehow needed to maintain the mother cells when new neuronal cells develop."

For More:

• Read the full article published in PLoS Biology
• Learn more through a release from St. Jude’s Children Research Hospital
• Prox1 Wikipedia page
• Prox1 Gene - GeneCards
• Order the book, The Dentate Gyrus: A Comprehensive Guide to Structure, Function, and Clinical Implications, 163
• Dentate gyrus Wikipedia page