Homeobox protein MSX-2 is a protein that in humans is encoded by the MSX2 gene.[4][5][6]
This gene encodes a member of the muscle segment homeobox gene family. The encoded protein is a transcriptional repressor whose normal activity may establish a balance between survival and apoptosis of neural crest-derived cells required for proper craniofacial morphogenesis. The encoded protein may also have a role in promoting cell growth under certain conditions and may be an important target for the RAS signaling pathways. Mutations in this gene are associated with parietal foramina 1 and craniosynostosis type 2.[6] Msx2 is a homeobox gene localized on human chromosome 5 that encodes a transcription repressor and activator (MSX-2) responsible for craniofacial and limb-bud development. Cells will express msx2 when exposed to signaling molecules BMP-2 and BMP-4 in situ.[7] Expression of msx2 leads to the proliferation, migration and osteogenic differentiation of neural crest cells during embryogenesis and bone fracture.[8] It is well documented that expression of cell-cell adhesion molecules such as E-cadherins will promote structural integrity and an epithelial arrangement of cells, while expression of N-cadherin and vimentin promote mesenchymal arrangement and cell migration.[9][10] Msx2 downregulates E-cadherins and upregulates N-cadherin and vimentin which indicates its role in inducing epithelial mesenchymal transition (EMT). Germline knockout mice have been created for this gene (Msx2 +/-) in order to examine functional loss.[11] Clinical studies on craniosynostosis, or the premature fusion of cranial structures, have shown the condition to be genetically linked to mutation in the msx2 homeobox gene.[12]
Msh homeobox 2 has been shown to interact with DLX5,[13] DLX2[13] and MSX1.[13]