MSX1 Case Study

Although diet and hygiene play important roles in keeping your teeth in good shape, crowding, bite and/or alignment issues due to genetics can also have a big impact on the condition of your teeth.

Molecular Cell Biology, 7th Edition, 2013, Lodish, Berk, Kaiser, Krieger, Bretscher. Ploegh, Amon, and Scott. W.H. Freeman and Company (ISBN-13: 978-1-4292-3413-9)

The oligonucleotide antisense matches complementary to the region 107–128 of the human Smad7 mRNA sequence, and its

Cosegregation of the phenotype with a heterozygous stop mutation in the homeodomain has been revealed through direct sequencing and restriction-enzyme analysis. In a study histological analysis of Msx1-knockout mice, combining a finding of Msx1 expression in mesenchyme of developing nail beds, revealed that both tooth development as well as nail development were disrupted. A nonsense mutation in MSX1 causes TNS and Msx1 is critical for both tooth and nail development as both develop via epithelial-mesenchymal

LOX is the major cross-linking enzyme in the extracellular matrix of blood vessels, and loss of its activity results in blood vessel dilation and rupture. Even though there is no known human disease associated with an alteration in the LOX gene, a variety of genetic disorders had been linked to this mutation. Examples of these are Menkes disease, occipital horn syndrome, Thoracic Aortic Aneurysm and Dissection (TAAD), among others.

Studying the interactions of Runx2 and RNAPII with promoters, the experiment demonstrated that 9–10% of genes in the human genome may be regulated by Runx2 in osteosarcoma cells (van der Deen et al., 2012). Runx2 is bound to over 2,000 genes that are actively transcribed based on co-interactions with polymerase (van der Deen et al., 2012). Data also demonstrated that Runx2 interacts with inactive genes that lacked RNAPII (van der Deen et al., 2012). These results confirmed hypothesis that Runx2 is a bi-functional regulator, activating or repressing transcription (van der Deen et al., 2012). An interesting result of this study involved Runx2’s influence on genes involving cell adhesion and motility (van der Deen et al., 2012). Combining data from the immunprecipation and gene expression profiles with siRNA, researchers concluded target genes can be both up-regulated and down-regulated with Runx2 depletion (van der Deen et al., 2012). This result also supports Runx2’s role as a bi-functional regulator of expression in these cells. Depletion of Runx2 decreased motility of U2OS cells (van der Deen et al., 2012). After identifying Runx2 target genes involved in motility, one can concluded depletion of Runx2 lowers cell motility in osteosarcoma cells (van der Deen et al., 2012). All in all, Runx2

The Pitx2 protein is a bicoid-related homeodomain transcription factor involved in left-right asymmetric cardiogenesis as well as development of eye and craniofacial regions (Hjalt et al., 2000). Most interestingly, experimental murine models utilizing targeted loss of Pitx2 function resulted in severe cardiovascular defects including transposition of the great arteries,

The second stage occurs during the outward growth of the distal limb regions which depends greatly on sonic hedgehog expression at week 6 day 52 is when hand is fully formed. In both stages HOXD genes are critical since they are involved in initiation of shh expression during the earlier stage and mediation of shh signaling from within the limbs during the second stage. The resulting phenotype of HOXD13 mutants display limb malformations. There is much fewer missense and nonsense mutations in HOXD13 and the most common mutation is the addition of 7-14 in the N-terminal polyalanine repeats of the HOXD13 gene. When the gene is abnormal from the polyalanine repeat mutation, it produces an abnormal protein which destabilizes the normal protein confirmation, causing aggregation. Once this occurs, it halts the protein translocation which occurs from the cytoplasm to the nucleus where it acts as a transcription factor. Additionally, the size of the polyalanine repeats directly correlates with the severity of

Vertebrates, including mice, have Hox genes that are homologous to those of the fly, and these genes are clustered in discrete locations with a 3'-to-5' order reflecting an anterior to posterior order of expression. There are several differences between the mouse and fly Hox genes, however. One obvious difference is that there are more Hox genes on the 5' side of the mouse segment; these correspond to expression in the tail, and flies do not have anything homologous to the chordate tail. Another difference is that, in the mouse, there are four banks of Hox genes: HoxA, HoxB, HoxC, and HoxD. Vertebrates have these parallel, overlapping sets of Hox genes, which suggest that morphology could be a product of a combinatorial expression of the genes in the four Hox clusters.

The transcription factor Otx2 is prevalently detected in TH+ neurons located ventral–medial VTA neurons, and this distribution is gradually decreased in the central and dorsal–lateral VTA. It has also been shown that Otx2 is sporadically co-expressed with Girk2, while most if not all of the Otx2+ neurons are Calb+, and those located in the ventral VTA are also Ahd2+ (Di Salvio et al., 2010; Liang et al., 1996; Schein et al., 1998; Simeone et al., 2011). Despite this slight anatomical and molecular topography, the cell bodies are still largely intermingled within the midbrain nuclei (Fig 1).

Since Pax6 encodes a transcription factor that is involved in so many developmental pathways in the eye, pancreas, and nervous system, there is a wide spectrum of defects (Davis et al. 2008). The most common defect is aniridia (absence of the iris) which occurs due to a nonsense mutation

After the embryonic segments have formed, the Hox proteins determine the type of segment structures that will form on a given segment. Hox proteins thus confer segmental identity, but do not form the actual segments themselves. Hox genes are in gene clusters on the genome. In some living things like vertebrates and the various Hox genes are very close to each other on the chromosome in groups or

There is a high degree of genetic conservation between oral teeth and skin denticles —hard structures found on the outer surface of the shark. A deviation from this conservation is the expression of sox2 in teeth. The lack of the sox2 gene in skin denticles correlates with the lack of the regenerative capacity that is present in teeth. Sox2 is expressed in a band of epithelium from which both teeth and anteriormost taste-buds emerge. Taste buds, which predate the evolution of teeth, are constantly regenerated in all vertebrates and the emergence of teeth and taste buds from the same sox2-expressing region implies that the evolutionary precursors of the regenerative properties of shark teeth are related to the evolutionary precursors of the regenerative properties of shark taste buds. The combination of the gene regulatory network for odontodes (teeth and skin denticles) with the sox2 gene regulatory network for taste buds may have resulted in the evolution of regenerative teeth in the

The essential genes for normal tooth development which provide instructions for making proteins in the enamel are the AMELX, ENAM, and MMPO20 genes (Office of Rare Diseases Research). Proteins such as amelogenin, ameloblastin, and enamelin are critical for normal formation of the enamel (“Amelogenesis Imperfecta”). Enamel is the protective layer of tissue which protects the tooth from painful temperatures end chemicals (Office of Rare Diseases Research). “Enamel is 97% mineral by weight with approximately 1% protein and 2% water” (Wright). In Amelogenesis Imperfecta, the AMELX, ENAM, and MMP20 genes will be mutated and will alter the structure of the proteins or prevent any proteins from being made at all (“Amelogenesis Imperfecta”). This condition presents problems of socializing with others and discomfort, but they may be managed early by vigorous

Tooth regeneration is logically the ultimate dental treatment because humans only have two sets of teeth: the deciduous and permanent teeth. Extracted molars and baby teeth, which are routinely discarded everyday can have the potential to be used as a future medical treatment. Dental stem cells are among the more convenient cells to access and can provide a significant medical benefit, and a way to ensure a lifetime of permanent teeth. Regenerative dentistry is an emerging field likely to yield successful results with patients’ cells being banked for future use. Currently, the major challenges in whole tooth regeneration are to identify non-embryonic sources of cells with the same properties as tooth germ cells and to develop culture systems