How a Jawless Vertebrate Parasite Reveals Evolutionary Origins of the Thyroid

The thyroid, a vital endocrine organ in vertebrates, plays a key role in regulating metabolism and supporting growth. The first gland of both the nervous system and endocrine system to mature during an embryo's development, it initially evolved more than 500 million years ago out of a "primitive" precursor organ in chordates known as the endostyle. Now, using lamprey as a model organism, Caltech researchers have discovered how the evolutionary acquisition of a certain kind of stem cell, called a neural crest cell, facilitated the evolution of the endostyle into the thyroid.

The research is described in a paper appearing in the journal Science Advances on August 6. The work was conducted primarily in the laboratory of Marianne Bronner, the Edward B. Lewis Professor of Biology and director of Caltech's Beckman Institute.

Bronner's lab has long focused on neural crest cells and their role in vertebrate development and evolution. For example, the team previously examined the role of neural crest cells in forming the bony scales that protect sturgeon and other primitive fish, heart tissue in zebrafish and chickens, and neurons of the peripheral nervous system in lamprey.

"Neural crest cells seem to promote evolution," Bronner says. "When Darwin first proposed the theory of evolution, he was looking at the different shapes of beaks of finches on the Galapagos Islands. Beaks, in addition to other parts of the facial skeleton, happen to arise from neural crest cells. These cells seem to be able to change faster in evolutionary time than cells that are more ancient."

Vertebrates have neural crest cells, while invertebrates do not, further suggesting that these cells contribute to the evolution of complex body forms. The Bronner lab uses lamprey, slimy parasitic eel-like fish, as a model organism, because modern lamprey share some characteristics with the earliest vertebrates.

The new work, led by Senior Postdoctoral Scholar Research Associate Jan Stundl, examines how neural crest cells contribute to the development of the endostyle in the lamprey. The endostyle is an evolutionary novelty of chordates (animals in the phylum Chordata, which includes vertebrates), and lampreys are the only vertebrates that retain this organ, whose primary function is associated with filter feeding. In lampreys, the larval endostyle, composed of two lobes in a butterfly-like shape, transforms into thyroid follicles during metamorphosis. Stundl and the team traced how neural crest cells give rise to the five different cell types of the endostyle, two of which give rise to the thyroid follicles. Using the gene-editing technology CRISPR, they then genetically deleted genes associated with the neural crest developmental program in lamprey embryos. These modified lampreys failed to develop a fully formed endostyle, exhibiting instead only a primitive lobe resembling the simplified endostyle of invertebrate chordates. The findings suggested that neural crest cells are essential for driving the evolutionary transition from the chordate endostyle to the vertebrate thyroid gland.

"Mother Nature is 'smart,'" Stundl says. "Instead of evolving something new, you can rebuild from something already present, like the endostyle. Neural crest cells seem to play an important role in enabling this transition to happen. Without the neural crest, we might still be filter feeders."

The paper is titled "Acquisition of neural crest promoted thyroid evolution from chordate endostyle." In addition to Stundl and Bronner, Caltech co-authors are postdoctoral scholars Ayyappa Raja Desingu Rajan and Tatiana Solovieva; graduate student Hugo Urrutia; research associate Jana Stundlova; and former postdoctoral scholar Megan Martik now of UC Berkeley. Additional co-authors are Jake Leyhr, Tatjana Haitina, and Sophie Sanchez of Uppsala University; and Zuzana Musilova of Charles University in Prague, Czech Republic. Funding was provided by the National Institutes of Health, the European Union, Alex's Lemonade Stand Foundation, the American Heart Association, the Helen Hay Whitney Foundation, Swedish Research Council Vetenskapsrådet, and the European Synchrotron Radiation Facility. Marianne Bronner is an affiliated faculty member with the Tianqiao and Chrissy Chen Institute for Neuroscience at Caltech.