Zebrafish research points way to answers about human development

It’s not your parents’ lab rat
Zebrafish research points way to answers about human development

BY JADE BOYD
Rice News Staff

Zebrafish cost about a dollar at the pet store. They grow from eggs to hunting their own food in three days. Adults can lay up to 500 eggs at once… and you have more in common with them than you think.

“For all their differences, humans and zebrafish aren’t that dissimilar,” said Rice University zebrafish expert Mary Ellen Lane. “For every zebrafish gene we isolate, there is a related gene in humans.”

JEFF FITLOW

Mary Ellen Lane is using zebrafish to explore how the brain and central nervous system develop.

Which is why zebrafish — like rats and fruit flies before them — are becoming regular contributors to research on human health ranging from cancer to cocaine addiction. For example, zebrafish were used in a landmark 2005 study that led scientists to the human gene that regulates skin color.

Lane, assistant professor of biochemistry and cell biology, is now using her zebrafish to explore one the major unexplained areas in developmental biology — how the brain and central nervous system develop.

It helps that zebrafish embryos grow from just a single cell to having a forebrain, hindbrain, spinal column and eye within a scant 24 hours. It also helps that the embryos are transparent and develop outside their mothers’ bodies — and can thus been seen under a microscope at every step of their development.

“It’s a beautiful organism for experiment,” Lane said. “It develops in a very regular way, so any abnormality is easy to spot, even for undergraduates with only a few days training.”

JEFF FITLOW

Zebrafish are becoming regular contributors to research on human health ranging from cancer to cocaine addiction.

In biology, the term “development” refers to the process whereby a single cell transforms itself into a complex, multicellular being with structures like organs and limbs that work in a coordinated fashion. Since every cell in the organism contains the same genes, whether a cell becomes a brain cell or a heart cell depends on which of those genes are expressed and in what order.

Lane, graduate students Catherine McCollum and Shivas Amin, and undergraduate Philip Pauerstein recently zeroed in on a gene called LMO4 that’s known to play roles in both cell reproduction and in breast cancer.

Using the tools of biotechnology, the team studied zebrafish that couldn’t transcribe the LMO4 gene, and they observed marked enlargement in both the forebrain and optical portions of the embryos. When they overexpressed the LMO4 gene, making more protein than normal, those same areas shrank. The study will appear later this year in the journal Developmental Biology.

JEFF FITLOW

Dan Wagner and Lane won funding from Rice’s Faculty Initiatives Fund to hire a research scientist to oversee collaborative projects with partners in the Texas Medical Center.

“The study suggests that LMO4 independently regulates two other genes that promote growth in those areas of the embryo,” Lane said. “It fills in another piece of the bigger picture of what’s going on during neurological development.”

Lane established Rice’s zebrafish program six years ago. She said the program got a major boost in 2003 when fellow zebrafish researcher Dan Wagner joined the BCB faculty. Most recently, Wagner and Lane won funding from Rice’s Faculty Initiatives Fund to hire a research scientist to oversee collaborative projects with partners in the Texas Medical Center (TMC).

Wagner and Lane’s facility — which houses 18,000 zebrafish and employs a full-time fish caretaker — is capable of supporting more joint projects with TMC medical researchers, Wagner said. The problem has been lack of staff.

“The seed funding from the administration will allow us to hire a qualified researcher who’s dedicated to overseeing these collaborative programs,” Wagner said. “The interest from the medical center has always been there, and we believe this will allow us to build a self-sustaining program that will, in time, attract plenty of outside funding.”