Cultivator of Brain Parts

An ambitious researcher wrestles with some of the grand challenges of neural development

Ali is more hopeful. In April, his team reported11 that it had improved the vision of partially blind mice using transplants of photoreceptor precursor cells taken from mice a few days old. Ali and another of Sasai's collaborators, Masayo Takahashi at the RIKEN Center for Developmental Biology, are starting to extract sheets of photoreceptors that have been grown using Sasai's methods and transplant them into mice; Takahashi plans to transplant them into monkeys by the end of the year. Both are cagey about their early results, but Takahashi says that in mice, the transplanted photoreceptors “survived well”.

Hormonal challenge
Sasai has set his sights on more complex neural tissues. Last November, he reported3 the formation of a part of the pituitary gland — his “most complicated” tissue yet. In the embryo, the pituitary gland arises when two different tissues integrate to form a pouchlike structure. Sasai managed to recapitulate this in vitro partly by starting out with more than three times more embryonic stem cells than he had used to grow a mouse retina; the adjustment seems to increase the levels of signals that the cells exchange. When transplanted into mice in which the pituitary glands had been knocked out, the rudimentary organs restored the endocrine system and saved the mice. This work, too, might eventually provide a supply of pure, specialized cells, which could be used to treat endocrine disorders.

Sasai hopes to improve on his early efforts by growing a better pituitary gland, equipped with a blood supply; a cerebral cortex with all six layers of tissue; and photoreceptors mature enough to detect light. But his next major task is to culture a cerebellum, which will involve growing and integrating three tissues of different embryonic origins. The matchmaker is already at work, trying to conjure up the right atmosphere. “When a boy meets a girl, they start their own story — but not in a large auditorium full of people,” he says. “You need to put them on a beach or in a disco. Our system is simply going to create this environment.”

What Sasai plans to take on after the cerebellum is a secret, but he hopes eventually to encompass the whole brain. He does not mean building one — that would be enormously difficult and ethically fraught. Instead, he wants to work out how brain parts, with their remarkable capacity for autonomous growth and organization, combine and fold into a structure of such tremendous complexity.

“I don't want to be a parts-maker, making more and more tissues,” says Sasai. “I always want something conceptually different.”

This article is reproduced with permission from the magazine Nature. The article was first published on August 22, 2012.

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