Msx1 modulates the Pax9-null cardiovascular phenotype

PhD ThesisDevelopment of the aortic arch arteries from the pharyngeal arch arteries is a complex process requiring the interaction of several tissue types and tightly regulated gene expression during embryogenesis. In this work, the role of transcription factor Pax9 in cardiovascular development was investigated using transgenic mice, imaging techniques and gene expression analysis. Pax9 is specifically expressed in the pharyngeal endoderm at mid-embryogenesis, and Pax9-null mice die at birth from defects in the formation and remodeling of the 3rd and 4th pharyngeal arch arteries resulting in absent common carotid arteries, aberrant right subclavian artery and interrupted aortic arch. The aim of the work presented in this thesis was to identify genes that potentially acting in the same genetic regulatory network as Pax9 to control cardiovascular development. The transcription factor Msx1 was selected as this was shown to interact with Pax9 in tooth development, and transgenic mice lacking Msx1 and Msx2 display cardiovascular defects. Surprisingly, this analysis shows that mice simultaneously null for Pax9 and heterozygous for Msx1 have a significantly reduced incidence of aortic arch defects compared to Pax9 –/– mice. Although Pax9 and Msx1 proteins can interact during tooth formation, the expression of these two genes does not overlap in the pharyngeal arches, with Msx1 being expressed in neural crest cells. Immunohistochemistry labelling revealed that more neural crest cells were present within the 3rd pharyngeal arch of Pax9 –/–;Msx1+/– embryos compared to Pax9 –/– embryos, which suggesting a role for these cells in protecting the 3rd pharyngeal arch artery from regressing as observed in Pax9 –/– embryos. In addition, a thick layer of smooth muscle around the 3rd PAA in Pax9 –/–;Msx1+/– embryos compared to Pax9 –/– embryos was observed, , all together indicating that neural crest cells differentiate to smooth muscle in Pax9 –/–;Msx1+/– embryos and this help protect and support the 3rd PAA during remodeling. Our data therefore show that Msx1 heterozygosity appears to modulate the Pax9-null cardiovascular phenotype by a yet unrecognized mechanism.scholarship from Yarmouk Universit

Measurement of the quadriceps (Q) angle with respect to various body parameters in young Arab population.

The quadriceps angle (Q angle), formed between the quadriceps muscles and the patella tendon, is considered clinically as a very important parameter which displays the biomechanical effect of the quadriceps muscle on the knee, and it is also regarded a crucial factor for the proper posture and movement of the knee patella. The Q angle is routinely and regularly used as an assessment parameter during the diagnosis of many knee-related problems, including the anterior knee pain, osteoarthritis, and degenerative knee disorders. This study had been conducted so as to measure the normal Q angle values range in the Arab nationalities and determine the correlation between Q angle values and several body parameters, including gender, height, weight, dominant side, and the condylar distance of the femur. The study includes 500 healthy young Arab students from the Yarmouk University and Jordan University of Science and Technology. The Q angle of those volunteers was measured using a universal manual Goniometer with the subjects in the upright weight-bearing position. It was found that Q angle was greater in young women than young men. Also, the analysis of the data revealed an insignificant increase in the dominant side of the Q angle. In addition, the Q angle was significantly higher in the taller people of both sexes. However, the Q angle did not present any considerable correlation with weight in the study population; conversely, it was clearly observed that there was a link with the condylar distance of the femur in both sexes. It was also noticed that the Q angle increased remarkably when there was an increase in the condylar distance. Consequently, it turned out that the gender, height, and the condylar distance were momentous factors that had impact on the Q angle in our study samples. However, weight and dominancy factors did not show to have any influence on the values in our study

Msx1 haploinsufficiency modifies the Pax9-deficient cardiovascular phenotype

International audienceBackground: Successful embryogenesis relies on the coordinated interaction between genes and tissues. The transcription factors Pax9 and Msx1 genetically interact during mouse craniofacial morphogenesis, and mice deficient for either gene display abnormal tooth and palate development. Pax9 is expressed specifically in the pharyngeal endoderm at mid-embryogenesis, and mice deficient for Pax9 on a C57Bl/6 genetic background also have cardiovascular defects affecting the outflow tract and aortic arch arteries giving double-outlet right ventricle, absent common carotid arteries and interruption of the aortic arch. Results: In this study we have investigated both the effect of a different genetic background and Msx1 haploinsufficiency on the presentation of the Pax9-deficient cardiovascular phenotype. Compared to mice on a C57Bl/6 background, congenic CD1-Pax9-/mice displayed a significantly reduced incidence of outflow tract defects but aortic arch defects were unchanged. Pax9-/mice with Msx1 haploinsufficiency, however, have a reduced incidence of interrupted aortic arch, but more cases with cervical origins of the right subclavian artery and aortic arch, than seen in Pax9-/mice. This alteration in arch artery defects was accompanied by a rescue in third pharyngeal arch neural crest cell migration and smooth muscle cell coverage of the third pharyngeal arch arteries. Although this change in phenotype could theoretically be compatible with post-natal survival, using tissue-specific inactivation of Pax9 to maintain correct palate development whilst inducing the cardiovascular defects was unable to prevent postnatal death in the mutant mice. Hyoid bone and thyroid cartilage formation were abnormal in Pax9-/mice. Conclusions: Msx1 haploinsufficiency mitigates the arch artery defects in Pax9-/mice, potentially by maintaining the survival of the 3rd arch artery through unimpaired migration of neural crest cells to the third pharyngeal arches. With the neural crest cell derived hyoid bone and thyroid cartilage also being defective in Pax9-/mice, we speculate that the pharyngeal endoderm is a key signalling centre that impacts on neural crest cell behaviour highlighting the ability of cells in different tissues to act synergistically or antagonistically during embryo development