Study Clarifies Role of Hyaluronan in Cleft Palate Formation

Published September 2019 | Journal of Dental Research

Cleft palate is a common birth defect impacting about one in 1,000 live births. Even with surgical treatment, many individuals face long-term health implications.

In mammals, during embryonic development the palate arises from the maxillary process and grows down-ward to form a pair of palatal shelves flanking the developing tongue. These shelves then reorient horizontally above the tongue, grow towards each other and fuse at the middle to become the palate.

“Most cleft palate cases result from disruption or failure in palatal shelf reorientation,” says Yu Lan, PhD. “But the developmental mechanism driving palatal shelf elevation is not well understood.”

A prevailing hypothesis suggested a region-specific accumulation of hyaluronan plays a major role in PS elevation. A study led by Lan clarifies how the process works.

Using multiple lines of mouse models combined with embryonic maxillary explant culture assays, the study showed that Has2, one of three hyaluronan synthases in mammals, is responsible for hyaluronan synthesis and accumulation in the developing palatal shelves. The team further demonstrated that inactivating Has2 throughout the craniofacial mesenchyme caused cleft palate and micrognathia, but specific inactivation of Has2 in the palatal mesenchyme cells did not block palatal shelf elevation. However, the experiment contradicts the longstanding prevailing theory of a direct role for hyaluronan in palatal shelf elevation.

“We are happy our results represent a major milestone in the field of palate development research,” says Lan, lead author on the study. The results and conclusions have been corroborated by independent study by other researchers at University of Washington, and work continues at Cincinnati Children’s to better understand the mechanisms regulating palatal shelf elevation and palate development using other mutant mouse models.