Osr2 Transcription Factor Plays Key Role in Palate Development

Published July 21, 2017 | Journal of Dental Research

Researchers have long tried to untangle the causes and pathogenic mechanisms of cleft palate, one of the most common birth defects worldwide.

Here, scientists in the divisions of Plastic Surgery and Developmental Biology have zeroed in on the molecular mechanisms involving Osr2, a transcription factor encoding gene that affects palate development.

The team previously had shown that Osr2 is specifically activated in nascent palatal mesenchyme cells. They also generated Osr2 knockout mice that produced offspring born with cleft palate.

In this study, the team sheds new light on the molecular mechanisms controlling palate development through whole transcriptome RNA sequencing analyses of Osr2 mutant and wild-type mice. They found that expressions of more than 130 genes were significantly altered in the mutant tissues.

“Our data reveal, for the first time, that the Osr2 transcription factor regulates several distinct molecular pathways driving palate morphogenesis and cell differentiation,” says senior author Yu Lan, PhD.

One surprise: Expression of several members of Class 3 Semaphorins (Sema3s) was dramatically increased in the palatal mesenchyme in the mutant embryos. Sema3s are secreted proteins that regulate neuronal and vascular cell migration.

“These findings suggest,” Lan says, “that, in addition to regulating palatal shelf growth, the Osr2 transcription factor might play a key role in palatal innervation and palatal vascular morphogenesis.”

New preliminary data show a dramatic disruption of palatal innervation in Osr2 mutant mice, a largely unchartered area of research that Lan and her team are exploring.