Academia Sinica researchers said they have found a protein that functions as a key regulator of brain size and neuron generation, with the results of their research having the potential to advance the study of molecular mechanisms in the cerebral cortex and hereditary brain diseases.
A team led by Academia Sinica research fellow Chou Shen-ju (周申如) and College de France professor Jonathan Touboul identified a transcription factor — a protein that binds to specific DNA sequences and controls the rate of transcription of genetic information from DNA to RNA — LHX2, which might control the timing of neurogenesis — the development of nerves, nervous tissue or the nervous system — and the size of the cerebral cortex.
In experiments with mice, the team found that once LHX2 is removed from progenitor cells in the cerebral cortex during embryonic development, cortical neurons are generated prematurely, which results in a smaller cerebral cortex — about 50 percent of normal brain size — and a diminished number of neurons, Chou said.
The cerebral cortex is the most highly evolved brain structure and is responsible for the perception of sensory stimuli, the execution of motor activity, cognition and consciousness, Chou added.
The team found that LHX2 is required for the Wnt signaling pathway, a protein-based group of signal pathways that carry external signals into cells, to maintain cortical progenitor proliferation, she said.
The Wnt signaling fails to function without LHX2, while forcing Wnt activation in the cortical progenitors in mice results in a dramatically larger cortex with furrows, which is similar to a human brain, she said, adding that the Wnt signaling pathway was previously shown to be a key factor of brain size.
By modifying the timing of neurogenesis, the interplay between LHX2 and the Wnt signaling pathway appears to be a key regulatory mechanism in cortical development, Chou said.
The results of the study could further the understanding of neurodevelopmental diseases such as microcephaly — as microcephaly patients exhibit symptoms that are likely caused by a decreased number of neurons — while research explores how certain mechanisms ensure the correct number and types of neurons are generated, she said.
LHX2 interactions occur during embryonic development, so forced Wnt signaling pathway activation through LHX2 cannot be applied to grown humans, Chou said.
The team is trying to understand how different types of neurons are generated during cortical development, Chou said, adding that they might extend the research to infant brain development.
The study was published last month in the Proceedings of the National Academy of Sciences of the United States of America academic journal.
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