Novel Cleft Palate Discovery is Palate Pleasing

Novel Cleft Palate Discovery is Palate Pleasing

By Amanda Jiang ’21

Comparison between a newborn with a cleft palate (left) and a newborn who underwent normal development (right) (Source: Wikimedia Commons).

New research from the University of Utah indicates that newborns have a lower risk of developing cleft palates through manipulation of the PAX9 and Wnt signaling pathways. Preliminary data from mice that have undergone in-utero treatments offer support for this new method for preventing cleft palates, and further research regarding therapeutic solutions is in progress.

What is a cleft palate? Despite the name, a cleft palate is not a split in one’s appreciation of different tastes and flavors. Instead, it is a split in the roof of the mouth that affects many newborns¹.

During pregnancy, body tissue and cells develop on the right and the left side of the fetus, and join in the middle. However, in some cases, the tissue that makes up the lip does not merge, resulting in a cleft palate. This defect has been plaguing the lives of over 7,000 newborns every year². The problems associated with cleft palates are not easily solvable, resulting in lifelong treatments and surgeries for the child. A cleft palate can hinder a child’s growth by inhibiting normal feeding and speaking functions.

Researchers at the University of Utah were excited when their research about tooth formation led them to discover the importance of PAX9 and Wnt genes in development of cleft palates (talk about hitting two birds with one stone). PAX9 is usually found in fetal development and cancer growth, affecting development of organs, the skeleton, and teeth.³ The Wnt signaling pathway normally regulates stem cells and cell fate during development.⁴

Experiments showed that when mice lacked PAX9, there was a subsequent increase in Dkk1 and Dkk2, both of which are genes involved in embryonic development and inhibit the Wnt signaling pathway.⁵ Thus, by inhibiting Dkk1 and Dkk2, the Wnt pathway is restored, resulting in palate fusion.

Rena D’Souza, professor of Dentistry and University of Utah Health, tested this hypothesis and found that palate fusion was restored in all the mice pups treated with Dkk1 and Dkk2 inhibitors. The Dkk inhibitor restores the Wnt and PAX9 pathway. Even after monitoring the mice for 18 months following the treatment, there were no adverse health effects found.⁶

Not only does the lack of PAX9 lead to cleft formation, but PAX9 deficiency is also associated with a myriad of other health problems. These problems include defects in the hind limbs, which might translate into leg disabilities for children, as well as parathyroid and thymus gland defects. The Wnt treatment for cleft palates has not been found to solve these other problems, but it appears to be a step in the right direction for preventing pre-birth defects.

D’Souza and her team are continuing to investigate the phenomena caused by PAX9 and Wnt signaling inhibition to generate safe and effective therapies for babies with palate defects.

References:

1. “Cleft Palate.” Merriam-Webster, Merriam-Webster, 2017, www.merriam-webster.com/dictionary/cleft%20palate.
2. “How Common Cleft Lip Palate Statistics.” Cleft Resources, http://cleftresources.com/how-common-cleft-lip-palate-statistics.
3. “PAX9 Gene (Protein Coding).” GeneCards, Human Gene Database, www.genecards.org/cgi-bin/carddisp.pl?gene=PAX9.
4. “Wnt/β-Catenin Signaling Interactive Pathway.” Cell Signaling Technology, Jan. 2003, https://www.cellsignal.com/contents/science-cst-pathways-stem-cell-markers/wnt-catenin-signaling-interactive-pathway/pathways-wnt
5. “Dkk2 Gene (Protein Coding).” GeneCards, Human Gene Database, http://www.genecards.org/cgi-bin/carddisp.pl?gene=DKK2
6. University of Utah Health. “In-utero treatment reverses cleft palate in mice.” ScienceDaily. ScienceDaily, 13 September 2017. <www.sciencedaily.com/releases/2017/09/170913193050.htm>.