Cecilia Moens remembers the moment she became a developmental biologist. In high school, a teacher played a film of a chicken embryo evolving from a single cell into a scraggly, hatching bird. Set to the dramatic thrums of Beethoven’s “Egmont Overture,” the film compressed 21 days of development into nine whirlwind minutes. “It absolutely captivated me,” Moens says of the film Overture, which earned an Academy Award nomination in 1965.
Later, in college, Moens read a Scientific American article about master genes that control an organism’s development. The discovery of these powerful snippets of DNA, called Hox genes, ignited an explosion of interest in developmental biology as Moens finished college.
“Reading that article was step two in captivating me,” Moens says. She was fascinated to learn that Hox genes dictate where all the parts of an animal’s body appear. They’re pattern makers, and they work the same in all animals, from fruit flies to humans. This discovery—of the key role this family of genes plays in all organisms—was a “huge aha moment” in the field. “Finding the Hox genes started to answer the basic question of developmental biology, which is how you get patterns formed out of nothing, out of a single egg cell,” says Moens.
She’s been exploring that question ever since.
Despite the two formative events, though, it took Moens a while to realize that developmental biology was a viable career option. In college, she worked in labs studying DNA repair and mutagenesis, the processes that damage DNA and cause cancer and other problems. She thought she’d find work in that field.
Then the third and final formative event intervened: Moens spent time in the laboratory of Douglas Melton, the noted HHMI investigator at Harvard, whose lab swarmed with bright young scientists delving into the deep molecular questions of embryonic development. Moens’s fate was set.
“I was knocked out that there were people who for their entire career got to study developmental biology,” says Moens. “I was very interested in the topic, but I thought that studying developmental biology for your life would be like getting to eat dessert instead of dinner every day.” She laughs. “It was the best thing in the world.”
Moens decided to concentrate on brain development. She wanted to understand which genes transformed a homogeneous, undifferentiated epithelium, the forming neural tube, into an exquisitely patterned command and control center. She wanted to identify these genes based on what goes wrong when they’re mutated—a so-called forward genetic approach—and at that time the only vertebrate suited for that approach was the zebrafish, a model system established by George Streisinger and colleagues in Oregon in the 1980s.
Since then, Moens has established herself as a top zebrafish geneticist, developing techniques for breeding genetically altered larvae. Her lab now houses 20,000 zebrafish, many of them mutated in specific ways—a living genetic library for studying growth and development. With HHMI funding, Moens expanded the library and now creates mutant zebrafish for other researchers.
Along the way, she’s helped answer some basic questions. She used zebrafish mutants to uncover the regulation and function of the Hox genes in the growth and patterning of the zebrafish hindbrain, a linchpin segmented structure that controls movement and integrates sensory information. She revealed how razor-sharp boundaries form between these segments and how the vitamin A derivative retinoic acid, a potent teratogen that is essential for normal brain development, is actively controlled to allow the establishment of a fine-grained pattern in the hindbrain. More recently, she started to study how neurons migrate through this complex, patterned environment in the course of their normal development.
With zebrafish, the fate of these cells is an open book. “You can look at the genesis and behavior of neurons in real time, because of the rapidly developing, transparent embryo,” she says. “It’s extremely powerful. You just set the embryo up on a confocal microscope and start watching neurons being born and differentiating and moving.”
Moens sees zebrafish as an untapped resource for learning about human brain disorders, particularly problems originating in the brain stem, the oldest section of the brain. To that end, she’s trying to re-create in zebrafish the human genetic defect that leads to Joubert syndrome, a developmental disorder of the cerebellum. “There’s this incredible untapped potential for using transgenic zebrafish to gain an understanding of human neurodevelopmental disorders,” she says.
So while a chicken egg inspired her, Moens now spends her time peering at zebrafish embryos and producing colorful images of their growth. The filmmakers who long ago cut a tiny window in a chicken egg and pointed a camera at it would be intrigued.
