Novel Gene PRDM16 Plays Critical Role In Craniofacial Development

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Facial birth defects are conditions that are present in the baby at birth. These defects usually develop during the first trimester of pregnancy when organs are developing. Facial Cleft Birth Defects result from both gene mutations and environmental insults. Other causes include chromosomal abnormalities, exposure to infections in time of pregnancy, Rh incompatibility, folic acid deficiency, prolong exposure to radiation and hazardous chemicals, and alcohol and medication abuse. The gravity of the problem can be realized from the fact that in the United States, a baby is born with a facial cleft every hour, of every day of the year.

Cleft palate and cleft lip are some of the common birth defects. Cleft lip and cleft palate form when the tissues of the upper lip and the roof of the mouth fails to close. Within the first 7 weeks of conception, tissues of the upper lip and palate usually take place. When these tissues fail to close the gap, a cleft often forms. Some affected babies may only develop either a cleft lip or a cleft palate, but there are those that can have both defects. Due to the many variations in clefts, there is no specific cure or treatment for the cleft repair.

genes
Little is known of the factors governing differentiation of embryonic palate mesenchymal cells into bone or muscle. However, a transcription co-factor plays a critical role in development of the embryonic palate and it is known as PRDM16. It is a transcription factor originally described as being aberrantly activated in specific types of leukemia’s, and more recently as a master regulator of brown adipose tissue differentiation. Hence, identifying the cellular and molecular processes regulated by PRDM16 is an important step toward elucidating the underlying mechanisms important for normal embryonic development of the head and face.

There are over 100 genes, whose promoters are bound by PRDM16. These genes are linked to such diverse processes as chromatin remodeling and muscle and bone development. Chromatin immunoprecipitation followed by array analysis is utilized to identify genes regulated by Prdm16 in cells isolated from the secondary palate of embryos. Loss of Prdm16 expression leads to a significant decrease in the expression of osteopontin, a marker for bone formation, and an increase in the expression of Myf-4, a marker for muscle development. Hence, developmental processes regulated by this protein are important for palate development. This can be of great significance in understanding of birth defects leading to facial clefts.