Scientists identify gene regulating human brain development

Scientists from the University of Wisconsin-Madison have identified a single gene that seems to be a master regulator of human brain development, guiding undifferentiated stem cells down tightly defined pathways to becoming all of the many types of cells that make up the brain.

The new finding is important because it reveals the main genetic factor responsible for instructing cells at the earliest stages of embryonic development to become the cells of the brain and spinal cord.

Identifying the gene — known as Pax6 — is a first critical step toward routinely forging customized brain cells in the lab.

What”s more, the work contrasts with findings from animal models such as the mouse and zebrafish, pillars of developmental biology, and thus helps cement the importance of the models being developed from human embryonic stem cells.

The new work, conducted in the Waisman Center laboratory of UW-Madison neuroscientist Su-Chun Zhang, reveals the pervasive influence of Pax6 on the neuroectoderm, a structure that arises early in embryonic development and that churns out the two primary forms of brain cells — neurons and glial cells — and the hundreds of cell subtypes that make up the human brain.

“This is a well-known gene. It”s been known for a long time from work in mice and other animals, but what Pax6 does in human development isn”t very well known,” Zhang said.

In animals, the gene is known to play a role in the development of the eye and is seen in some neural cells. In the human cells used in the new Wisconsin study, Pax6 was observed in virtually all of the cells of the neuroectoderm.

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“The fact that Pax6 is uniformly expressed in all human neuroectoderm cells was a surprise. This is a phenomenon that is a departure from what we see in animals. It seems that in the earliest stages of development, human cells are regulated by different processes,” Zhang said.

The finding may help explain why the human brain is larger and, in many respects, more advanced than what is observed in other species.

The study appears in the journal Cell Stem Cell.

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