New research has shed some light on the development of the human brain, scientists said yesterday.
While the mechanism by which human brain size is determined is still relatively unknown, a study of gene abnormality in primary microcephaly (MCPH) patients has revealed how cell organelle centrioles may affect the thickness of the cerebral cortex, said Tang Tang (唐堂), a Research Fellow at Academia Sinica’s Institute of Biomedical Sciences.
“MCPH patients are characterized by a head circumference that is three standard deviations smaller than the norm,” Tang told a press conference at the National Science Council yesterday.
In addition to having a substantially smaller cerebral cortex and central nervous system than healthy individuals, “in most cases, MCPH patients also have mild to severe mental retardation,” Tang said.
Though the exact reason people develop MCPH is unknown, so far a total of seven genes have been found to lead to MCPH. Four of them, named MCPH1, MCPH3, MCPH5 and MCPH6 [called centrosomal P4.1-associated protein (CPAP), a gene discovered by Tang’s lab in 2000], have been singled out already, Tang said.
Of the four workable genes the researchers have found, three (MCPH3, 5, and 6) are located on the centriole, he said.
“In higher order animals, cell division includes DNA duplication as well as centriole duplication, but so far little is known about the latter,” Tang said.
What is known now is that centrioles assist the centrosomal protein recruiting process and in turn help promote the cell mitosis [cell division] process, he said.
In their study on MCPH patients, Tang’s team identified a mechanism in which centriole duplication is governed by CPAP, Tang said.
“[Our lab] discovered CPAP in 2000 and in 2005 another group of researchers found mutation of the gene leads to MCPH,” Tang said.
“In our new research, we found that insufficient CPAP protein levels in cells inhibited the duplication of the centrioles during neurogenic mitosis and in turn we deduce that the phenomenon causes a reduced number in the afflicted individual’s brain cells,” he said.
In other words, by having depleted CPAP proteins, people have smaller brains.
The team’s finding was published in this month’s edition of Nature Cell Biology.
While clinically almost all MCPH cases caused by CPAP abnormality demonstrate a CPAP deficiency, Tang’s team discovered that an excess level of CPAP in the cells also cause centriole replication to be abnormal.
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