Most compellingly, double knock-out of MMP-14 (MT1-MMP) and MMP-16 (MT3-MMP) results in a cleft palate in mice due to impaired growth of the palate shelves [29], which implies a role for proteolytic enzymes in mouse SP development even though no palate defects were reported for the single gene knock-out of either MMP-16 [29] or MMP-14 [30]. Here, MMP16 is linked to cleft palate.