Table 3.
MMP associated with palate development.
| Expression pattern in the palate |
Mouse mutant associated with cleft palate |
|||||||
|---|---|---|---|---|---|---|---|---|
| Extracellular metalloproteinases | Subtype/alternative name | Location | Detection methods | References | ECM substrates during palate development | Mouse mutants | Defects | References |
| MMPs | MMP-1/Collagenase-1 | Unknown | qRT-PCR | 24 | NR | NR | ||
| MMP-2/Gelatinase A | Before palate shelf elevation: in the palatal mesenchyme and basement membrane, intensified gradually in the nasal-medial part. During the palatal shelf elevation and the palatal shelf fusion: intensified gradually in the tip and nasal-medial part and MES After the palatal shelf fusion: strong in palatal mesenchyme around MES. |
qRT-PCR, IHC, ISH | 1-3,24,100,105 | Cleaves type I collagen | NR | |||
| MMP-3 | Extensively expressed in palatal mesenchyme, transiently upregulated in a subset of nasal palatal epithelial cells. | IHC | 100,102,106 | NR | NR | |||
| MMP-9/Gelatinase B | Extensively expressed in palatal mesenchyme, transiently upregulated while palatal shelves elevating and fusing. | qRT-PCR, IHC, ISH | Human and mouse:24,102,104 | Cleaves laminin | NR | |||
| MMP13 | Before palate shelf elevation: in the palatal mesenchyme and basement membrane, intensified gradually in the nasal-medial part. During the palatal shelf elevation and the palatal shelf fusion: intensified gradually in the tip and nasal-medial part and MES After the palatal shelf fusion: still strong in the nasal-medial mesenchyme and MES but decreased in other area. |
IHC, ISH | Mouse100,105,119 | NR | NR | |||
| MMP-14/Membrane Type 1-MMP (MT1-MMP) | Highly in MEE | IHC, ISH | 105 | NR | Double knockout of MMP-14 and −16 | 80% of double null of MMP-14 and −16 have a cleft palate | 107 | |
| MMP-16/Membrane Type 3-MMP (MT3-MMP) | Unknown | NR | Double knockout of MMP-14 and −16 | 80% of double null of MMP-14 and −16 have a cleft palate | 107 | |||
| MMP-25 | The tips of palatal epithelium and mesenchyme | IHC, ISH | 108 | NR | NR | |||
| TIMPs | TIMP-1 | Before palate shelf elevation: in the central and maxillary region of palatal mesenchyme During the palatal shelf elevation and the palatal shelf fusion: intensified gradually in the tip and nasal-medial part and MES; palatal basement membrane After the palatal shelf fusion: strong in the nasal-medial mesenchyme and MES but decreased in other area. |
IHC | 100 | NR | NR | ||
| TIMP-2 | Before palate shelf elevation: in the central and maxillary region of palatal mesenchyme During the palatal shelf elevation and the palatal shelf fusion: intensified within palatal mesenchyme; palatal basement membrane After the palatal shelf fusion: strong in the nasal-medial mesenchyme and future osteogenic sites. |
IHC | 100 | NR | NR | |||
| TIMP-3 | Palatal epithelium, transiently expressed in mid-oral and ventral-medial mesenchyme. | IHC | 100 | NR | NR | |||
| TIMP-4 | Oral mucosa | IHC | 104 | NR | NR | |||
| ADAMTS | ADAMTS9 | Palatal capillary endothelium | ISH | 12 | Versican | Haploinsufficiendy of Adamts9 in Adamts20 mutant mice (Adamts9±;Adamts20bt/bt) | Complete cleft palate | 12 |
| ADAMTS20 | Palatal mesenchyme | ISH | 12 | |||||
NR, not reported.
IHC, immunohistochemical staining.
ISH, in situ hybridization.