Scientists at the Salk Institute for Biological Studies have found that a growth factor called Fgf10 helps keep the brain's development on track.
The researchers say that just like a conductor cues musicians in an orchestra, this growth factor lets brain stem cells know that the moment to get to work has arrived, ensuring that they hit their first developmental milestone on time.
AdvertisementThe researchers say that their findings not only provide new insights into brain development, but also reveal a possible mechanism for the selective expansion of specific brain areas over the course of evolution, such as the greatly increased size of the frontal lobe in humans.
During embryonic brain development, stem cells in charge of building the cortex-the largest brain structure and seat of most higher cognitive functions- pass through a series of tightly regulated stages: from omnipotent stem cell to cortical progenitors cells capable of producing neurons.
"The timing of each of these transitions has critical implications for brain development, since minor changes in the proportion of progenitors exhibiting one or the other division mode at early stages will result in substantial changes in the number of neurons and the size of the cortex," says lead researcher Dr. Dennis O'Leary, a professor in the Molecular Neurobiology Laboratory.
Postdoctoral researcher and first author Dr. Setsuko Sahara initially started looking at the effects of deleting Fgf10 in mouse brain, but she quickly realised that the primary function of the growth factor was to regulate the differentiation of radial glia, progenitor cells that divide asymmetrically to produce a pair of unlike daughter cells.
According to her, this role of Fgf10 has significant implications for brain size, including the size of specific cortical areas.
"These mice had substantially enlarged brains, but the structure was perfectly fine," says Setsuko.
A closer look revealed that the transition from the expansion stage to the neurogenic phase- which produces all the neurons that will eventually form the six layers of the cortex-exhibited by cortical progenitors was delayed by approximately two days.
"As a consequence neuroepithelial cells keep multiplying generating a bigger pool of radial glia, which in turn produce more neurons ultimately resulting in a larger cortex," explains Sahara.
Interestingly, the increase in size was limited to the frontal cortex, showing that at the time the population of early progenitors was abnormally expanded in Fgf10 mutants, their area identity had been fixed.
"These findings demonstrate a direct mechanism employed during normal development to regulate brain size. These findings also have potential implications for how cortical areas have evolved. Selectively expanding the progenitor pool by Fgf10 regulation of the timing of radial glia differentiation could account for the selective expansion of the frontal cortex, which has been greatly expanded in humans and is thought to be important for evolving what are considered typically human traits," says O'Leary.
A research article describing the study has been published in the journal Neuron.