Worms Yield Insights into Brain Development

Expression pattern of 2 ZLI-like genes (in green and magenta) in the acorn worm embryo.Pani et al, courtesy of Nature.

Acorn worm embryos don't have anything resembling a human brain. But researchers have found that developing worms have patterns of gene activity similar to those that direct our own brain development. The discovery suggests that genetic programs in creatures living more than 600 million years ago formed a scaffold from which more complex systems evolved.

The vertebrate brain arises from tissue in the embryo called the neuroectoderm. Regional areas in this tissue called signaling centers organize complex gene expression patterns that drive formation of the central nervous system and brain. Three signaling centers key to vertebrate brain development are the anterior neural ridge (ANR), zona limitans intrathalamica (ZLI) and isthmic organizer (IsO).

Understanding how the complex vertebrate brain evolved has been a major research challenge. For insights, scientists have often looked to our closest relatives on the evolutionary tree: the urochordates (tunicates, or sea squirts) and cephalochordates (lancelets, eel-like animals that tend to live buried in sand). But genetic programs resembling the ANR, ZLI and IsO haven't been found in these creatures. Researchers have thus suspected that these complex programs first arose as vertebrate brains evolved.

A research team led by Drs. Chris Lowe and Ariel Pani of Stanford University and the University of Chicago aimed to test another idea: that the bases for the ANR, ZLI and IsO existed long ago but were lost along some branches of the evolutionary tree. They decided to look at hemichordates, which are further from vertebrates on the evolutionary tree than the urochordates or cephalochordates.

The scientists looked for ANR-, ZLI- and IsO-like gene expression patterns in the developing ectoderm of Saccoglossus kowalevskii, an acorn worm found in intertidal zones along the East coast. They then worked with researchers in Dr. Elizabeth Grove's lab at the University of Chicago to compare patterns of gene expression between acorn worm and mouse embryos. Their study was funded by NIH's Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institute of Neurological Disorders and Stroke (NINDS) and others.

In Nature on March 15, 2012, they reported finding patterns of gene expression that resemble all 3 vertebrate signaling centers. The researchers were also able to selectively suppress the activity of key developmental genes in these centers by injecting short interfering RNA. Many of the suppressed genes affected acorn worm development in ways similar to vertebrates.

“The closer we looked, the more similarities we found between these strange worms and vertebrate brains in their underlying molecular blueprints,” Lowe says. “This suggests that essential parts of these blueprints, previously thought to be unique to complex brains, have much earlier evolutionary origins.”

The researchers propose that signaling centers resembling ANR, ZLI and IsO initially directed general body plan organization. These ancestral signaling centers formed a genetic scaffold that was adapted and built upon over time to pattern the new structures of the vertebrate brain and nervous system.

“No one thought hemichordates would be that informative in understanding the origin of vertebrates,” Lowe says. “These findings remind us that modern animals are all at the 'tips of the branches' of the evolutionary tree.” To fully understand how we evolved, the researchers say, we need to look at all the branches.

—by Harrison Wein, Ph.D.