This image shows induced human neural crest cells. Human embryonic stem cells display neural crest characteristic expression after only five days of culture under WNT induction. Transcription factors SOX10 and PAX7 are seen in green and red, respectively. [García-Castro lab, UC Riverside.]
This image shows induced human neural crest cells. Human embryonic stem cells display neural crest characteristic expression after only five days of culture under WNT induction. Transcription factors SOX10 and PAX7 are seen in green and red, respectively. [García-Castro lab, UC Riverside.]

Scientists at the University of California, Riverside say they have developed a robust, fast, simple, and trackable method to generate neural crest cells. They believe their proposed technique can facilitate research in basic sciences and clinical applications alike.

“Our study provides a superb model to generate neural crest cells in just five days, starting from human embryonic stem cells or induced pluripotent cells, using a simple and well-defined media with all ingredients known and accounted for,” said Martín I. García-Castro, Ph.D., associate professor of biomedical sciences in the university's school of medicine and whose team led the study (“WNT/β-catenin signaling mediates human neural crest induction via a pre-neural border intermediate”) published in Development. “Our cost-effective, efficient, and fast protocol allows a better analysis of the relevant signals and molecules involved in the formation of these cells. Our results suggest that human neural crest cells can arise independently from and prior to the formation of mesoderm and neural ectoderm derivatives, both of which had been thought to be critical for neural crest formation.”

Neural crest cells arise early in the development of vertebrates, migrate extensively through the embryo, and differentiate to give rise to a wide array of diverse derivatives. Their contributions include a large proportion of our peripheral nerves, the melanocytes that provide skin color and protection from damaging UV light, as well as many different cell types in our face, including muscle, bone, cartilage, and tooth-forming cells.

The proper functioning of these cells is critical for human development and health. When neural crest biology fails, various birth defects and illnesses such as cleft lip/palate, Hirschsprung, and Waardenburg syndromes, melanoma and neuroblastoma result. A better study of these cells is crucial, therefore, to aid in clinical efforts to diagnose and treat such conditions.

Dr. García-Castro's previous work on birds already challenged the dogma suggesting that neural crest cells form without mesodermal or neural contribution. Unpublished results from his lab have also confirmed the same using rabbit embryos as a mammalian model.

With regard to identifying specific molecules and their roles during neural crest cell formation, Dr. García-Castro's new work demonstrates the critical role played by WNT and highlights contributions from protein families called FGFs and BMPs. WNT proteins are signaling molecules that regulate cell-to-cell interactions during development and adult tissue homeostasis. The FGF protein family controls a wide range of biological functions. BMPs induce the formation of bone and cartilage and form tissues throughout the body.

“Our work provides strong evidence of the critical and initiating role of WNT signals in neural crest cell formation, with later contributions by FGF and BMP pathways,” said Dr. García-Castro, emphasizing that the proper function of neural crest cells is essential for human development and health. “The study of these cells is essential to improve clinical efforts to diagnose, manage, and perhaps prevent diseases and conditions linked to them, and our lab has already launched efforts toward facial clefts—lip and/or palate—and melanoma, and we hope to make substantial progress in both areas thanks to this novel protocol.”








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