Scientists at the Stowers Institute for Medical Research have come up with an explanation on how a gene underpins the prenatal development of the nervous system.
Their study sheds light on the mechanisms which regulate the process, that requires coordination of differentiation of immature neural cells with the cycle of cell division that increases their numbers.
The researchers used gain- and loss-of-function mutations in mice to isolate novel roles for the mouse Cux2 gene in regulating neurogenesis.
They found that Cux2 directs neuroblast development, neuronal differentiation, and cell-fate determination in the spinal cord by coupling progression through the cycle of cell division with differentiation of neural cells.
According to the researchers, the gene does so by activating two key neurogenic determinants, Neurod and p27Kipl.
"We were excited to uncover, for the first time, multiple functional roles for a Cux-like homeodomain transcription factor in regulating key aspects of spinal cord neurogenesis," said Angelo Iulianella, Senior Research Associate and first author of the study.
"The demonstration that Cux2 integrates cell-cycle progression with neural progenitor differentiation and cell-fate determination provides a much clearer picture of the complex process of neurogenesis," Iulianella added.
Paul Trainor, Associate Investigator and senior author of the study, said: "The impact of cell cycle length on the formation of interneurons versus motoneurons was a surprising finding. Ongoing work involves global proteomic analyses aimed at identifying the complete set of Cux2-interacting partners. We believe these efforts will be essential to understanding how Cux2 elicits its multiple functions during neurogenesis."
The researchers say that further analysis of Cux2 will make it possible to extend their findings not only to spinal cord development, but also to the mammalian cortex where Cux genes demarcate specific upper layers of cortical neurons, and may have played a role in the expansion and increased complexity of the cortex during evolution.
The study will be published in the February 15 issue of Development.