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Gene Review

MSX2  -  msh homeobox 2

Gallus gallus

Synonyms: HOX-8, Msx-2
 
 
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High impact information on MSX2

  • IGF-I and insulin, but not FGFs, also cause the thin apical ectoderms of wl and ll limb buds to thicken and form structures that grossly resemble normal AERs and, moreover, induce high level expression of Msx-2 in these thickened AER-like structures [1].
  • Wl and ll limb buds lack thickened AERs capable of promoting limb outgrowth, and their thin apical ectoderms fail to express the homeobox-containing gene Msx-2, which is highly expressed by normal AERs and has been implicated in regulating AER activity [1].
  • The implications of these results to the relationships among the wl and ll genes, IGF-I/insulin, FGFs, Msx-2 and Msx-1 in the regulation of limb outgrowth is discussed [1].
  • Maintenance of GHox-8 expression by the anterior mesoderm appears to be independent of the presence of the apical ridge.(ABSTRACT TRUNCATED AT 250 WORDS)[2]
  • Role of the chicken homeobox-containing genes GHox-4.6 and GHox-8 in the specification of positional identities during the development of normal and polydactylous chick limb buds [3].
 

Biological context of MSX2

  • In the proximal posterior periphery of the wing bud at these later stages of development, expression of GHox-8 is limited to a small region in the mid-proximal periphery corresponding to the posterior necrotic zone in which programmed cell death is occurring [4].
  • MSX2 expression in the apical ectoderm ridge is regulated by an MSX2 and Dlx5 binding site [5].
  • To test this hypothesis, we have isolated the chicken Msx-2 gene and have tested the ability of various regions of the gene to target expression of LacZ reporter gene to specific regions of the limbs of transgenic mice [6].
  • Identification of a spatially specific enhancer element in the chicken Msx-2 gene that regulates its expression in the apical ectodermal ridge of the developing limb buds of transgenic mice [6].
  • The vertebrate homeobox genes Msx-1 and Msx-2 are related to the Drosophila msh gene and are expressed in a variety of tissues during embryogenesis [7].
 

Anatomical context of MSX2

  • At early stages (stages 20-21) of chick limb development when positional values along the anterior-posterior (A-P) axis are being specified, GHox-8 is expressed in high amounts in the anterior mesoderm of the wing bud [4].
  • In the developing chick limb bud, Msx-2 is expressed in the apical ectodermal ridge, which plays a crucial role in directing the growth and patterning of limb mesoderm [6].
  • The timing of Msx-2 expression suggests that it plays a role in conduction system tissue formation and that it identifies precursor cells of this specialised myocardium [7].
  • In the present study the expression of GHox-7 and GHox-8 has been examined by in situ and dot blot hybridization in the developing limb buds of limbless mutant chick embryos [8].
  • Despite down-regulation in neural crest cells, the onset of Msx-2 expression in the facial prominences at stage 18-20 was normal [9].
 

Associations of MSX2 with chemical compounds

  • Following retinoid treatment, Msx 1 and Msx 2 transcripts are rapidly down-regulated in upper beak primordia where outgrowth is inhibited, but remain largely unchanged in lower beak primordia, where outgrowth is unaffected [10].
  • Alterations in Msx 1 and Msx 2 expression correlate with inhibition of outgrowth of chick facial primordia induced by retinoic acid [10].
 

Other interactions of MSX2

  • Expression of the chicken homeobox-containing gene GHox-8 during embryonic chick limb development [4].
  • The expression of Msx1 and Msx2 genes was maintained under the ridge indicating a good interaction between the interdigital cells, both dissociated and undissociated, and the apical ridge [11].
  • In situ hybridization of BMP-4 mRNA resolved to centers at R3 and R5 but Msx-2 resolved to the R2/3 border with only a faint smear from R5 to R6 [12].
 

Analytical, diagnostic and therapeutic context of MSX2

  • Northern blot hybridization indicates that transcripts for both Msx-1 (1.6 Kb) and Msx-2 (3 Kb) are present in the mandibular arch as early as stage 18 [13].

References

  1. IGF-I, insulin and FGFs induce outgrowth of the limb buds of amelic mutant chick embryos. Dealy, C.N., Kosher, R.A. Development (1996) [Pubmed]
  2. Apical ridge dependent and independent mesodermal domains of GHox-7 and GHox-8 expression in chick limb buds. Ros, M.A., Lyons, G., Kosher, R.A., Upholt, W.B., Coelho, C.N., Fallon, J.F. Development (1992) [Pubmed]
  3. Role of the chicken homeobox-containing genes GHox-4.6 and GHox-8 in the specification of positional identities during the development of normal and polydactylous chick limb buds. Coelho, C.N., Upholt, W.B., Kosher, R.A. Development (1992) [Pubmed]
  4. Expression of the chicken homeobox-containing gene GHox-8 during embryonic chick limb development. Coelho, C.N., Sumoy, L., Rodgers, B.J., Davidson, D.R., Hill, R.E., Upholt, W.B., Kosher, R.A. Mech. Dev. (1991) [Pubmed]
  5. MSX2 expression in the apical ectoderm ridge is regulated by an MSX2 and Dlx5 binding site. Pan, Z.Z., Kronenberg, M.S., Huang, D.Y., Sumoy, L., Rogina, B., Lichtler, A.C., Upholt, W.B. Biochem. Biophys. Res. Commun. (2002) [Pubmed]
  6. Identification of a spatially specific enhancer element in the chicken Msx-2 gene that regulates its expression in the apical ectodermal ridge of the developing limb buds of transgenic mice. Sumoy, L., Wang, C.K., Lichtler, A.C., Pierro, L.J., Kosher, R.A., Upholt, W.B. Dev. Biol. (1995) [Pubmed]
  7. Expression of homeobox genes Msx-1 (Hox-7) and Msx-2 (Hox-8) during cardiac development in the chick. Chan-Thomas, P.S., Thompson, R.P., Robert, B., Yacoub, M.H., Barton, P.J. Dev. Dyn. (1993) [Pubmed]
  8. Altered expression of the chicken homeobox-containing genes GHox-7 and GHox-8 in the limb buds of limbless mutant chick embryos. Coelho, C.N., Krabbenhoft, K.M., Upholt, W.B., Fallon, J.F., Kosher, R.A. Development (1991) [Pubmed]
  9. Locally released retinoic acid repatterns the first branchial arch cartilages in vivo. Plant, M.R., MacDonald, M.E., Grad, L.I., Ritchie, S.J., Richman, J.M. Dev. Biol. (2000) [Pubmed]
  10. Alterations in Msx 1 and Msx 2 expression correlate with inhibition of outgrowth of chick facial primordia induced by retinoic acid. Brown, J.M., Robertson, K.E., Wedden, S.E., Tickle, C. Anat. Embryol. (1997) [Pubmed]
  11. Morphogenetic potential of the chick leg interdigital mesoderm when diverted from the cell death program. Ros, M.A., Piedra, M.E., Fallon, J.F., Hurle, J.M. Dev. Dyn. (1997) [Pubmed]
  12. A paraxial exclusion zone creates patterned cranial neural crest cell outgrowth adjacent to rhombomeres 3 and 5. Farlie, P.G., Kerr, R., Thomas, P., Symes, T., Minichiello, J., Hearn, C.J., Newgreen, D. Dev. Biol. (1999) [Pubmed]
  13. Experimental analysis of Msx-1 and Msx-2 gene expression during chick mandibular morphogenesis. Mina, M., Gluhak, J., Upholt, W.B., Kollar, E.J., Rogers, B. Dev. Dyn. (1995) [Pubmed]
 
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