Drafts

    HOX genes, specifically HOXC genes and their homeodomains, are vital to the development of vertebrates. The HOXC genes function in cell differentiation, proliferation, and epithelial tissue development, with associations to lymphoma and club foot in humans (Gene Cards, 2019). Some studies have also indicated that the genes may be important in vertebrae (Carrasco, 1994) and other bone development such as craniofacial morphogenesis (Hirata, 2016). Mutations in these genes can often result in a homeotic mutation, where certain body parts end up growing where it is not usually grown, or a severe malformation of certain limbs and organs (Alvarado, 2016).

HOX genes specify the regions in an anterior-posterior axis of an animal. Because the organization of the body depends on these genes, a mutation in them often results in misformation of limbs and other body parts. Because HOX genes are highly conserved across species, making it useful in determining the phylogeny of species. However, the determination of the HOXC gene as an indicator of phylogeny across all vertebrae species is something that has not been examined as of now.

Another specific aim the proposal has is to isolate and characterize the expression of highly conserved genes identified in Specific Aim 1 from the Animalia kingdom. The expansion of our subject of interest from chicken, zebrafish, Xenopus, and newt to the Animalia kingdom will allow for the comparison of the HOX gene in all vertebrate and invertebrate animals, which is different from species to species. Characterization methods of our data include a phylogenetic tree and a heat graph of gene expression. A modified phylogenetic tree allows us to map where organisms may have originated based on HOX similarities. The phylogenetic tree will take into account the Animalia kingdom.

The statement motivated our group to propose that the HOX genes express little variation in vertebrae, and test the statement by knowing how consistent this data would be if we were to expand our subject of interest to a whole kingdom, rather than specific subjects used for their evidence (chicken, zebrafish, Xenopus, and newt). We will now look into HOX genes to see how similar or different expression of the HOX gene is throughout the Animalia kingdom.

The objective of our proposal is to create a phylogenetic tree examining the possibility of using the HOXC gene as an indicator of the phylogeny. One specific aim of the proposal is to identify highly conserved genes that are present in vertebrates. In preliminary work, we found that one example of a highly conserved gene is the BOP1 gene present in ribosomal DNA. Further research done on HOX genes has noted that the duplication of HOX clusters is shared by all vertebrae (Ruddle et al. 1994).

The objective of our proposal is to create a phylogenetic tree examining the possibility of using the HOXC gene as an indicator of the phylogeny. One specific aim of the proposal is to identify highly conserved genes that are present in vertebrates. In preliminary work, we found that one example of a highly conserved gene is the BOP1 gene present in ribosomal DNA. Further research done on HOX genes has noted that the duplication of HOX clusters is shared by all vertebrae (Ruddle et al. 1994). The statement motivated our group to propose that the HOX genes express little variation in vertebrae, and test the statement by knowing how consistent this data would be if we were to expand our subject of interest to a whole kingdom, rather than specific subjects used for their evidence (chicken, zebrafish, Xenopus, and newt). We will now look into HOX genes to see how similar or different expression of the HOX gene is throughout the Animalia kingdom.

This was also conducted on male mouse which show body weight fluctuations less obviously than women. The results of the study could have shown different results if it was done with female mice. Energy is very important for the function of our body, especially the brain. For example, if there is not enough glucose then action potentials cannot fire. Now what happens if you have an excess of energy, we would want to activate aMSH. If we are in the opposite situation, we would want to inhibit AgRP. Leptin is expressed in proportion to the amount of fat that you have. It has the ability to activitate aMSH or inhibit AgRP. ob/ob mutants are not able to activate the aMSH but also not inhibit the AgRP. Now lets say this was done to a Pomc neuron. This would cause the Pomc neuron to die and now the aMish neuron would not turn off satiety. Therefore they would never feel satiated. There was an increase in the amount that they ate but their phenotype in body weight changed much more slowly.

If you administered hDTR, known as deferiotoxin, to a mouse they would not respond. This is because the mouse is not responsive to human virus. The best way to get the virus into the mouse, would to package it into a virus shell and inject it into the mouse. The result from this injection would be the expression of Agrp, which would become infected with this toxin. For some background, Agrp inhibit the MCAR which shuts down the satiety neuron, which drives hunger. The phenotype of this injection would be lead for the receptor The hDTR would not connect to Agrp neurons and cause them to go through apoptosis. This would lead to a decrease in body weight. AgRP shuts off satiety neuron, which tells you that you’re full. This causes the mouse to stop eating and die of starvation. They feel satiented the whole time as there is not a receptor to shut it off. Within five days their food intake drops to 20% of the amount that they initially consumed. 

There are three ways the hypothalamus responds to sensory signals and maintains homeostasis. Humoral response stimulate or inhibit release of hormones through the pituitary. Visceromotor responses adjust the balance within the autonomic nervous system and the somatic motor response which stimulate behavior through the somatic system. There are many gene techniques to access the brain some of which include; are cre-expressing mouse lines and delivering viruses to anatomically to specific locations. These processes let us artificially manipulate the genes in the brain to see how they express themselves. In addition, we can do tract tracing by delivering engineered genes into the brain. In this way, we can activate neurons and turn them off to see how they affect behavior. We can then analyse the behavior that comes from this modification. Neurobio used to be based on just ecological literature but now we can add both the literature and these experiments to come to a clearer conclusion. Body weight regulation starts with looking at certain genes which are very rare. Mutations of the leptin gene lead to inability to control body weight. Deb gene is a gene that affects body weight. Diabetes is not only a genetic disorder but it is polygenic, multiple genes associated with each other. These genes need external influence to become completely expressed.

Mollecularly, cancer is typically associated with gain of function mutations in oncogenes as well as loss of function mutations in tumor-suppressor genes. One gene in particular has been associated with a wide variety of cancers, PIK3CA. PIK3CA is a gene responsible for PI3K, a downstream protein in RTK signaling that converts PIP2 to PIP3, thus continuing the signal transduction pathway. However, in double PIK3CA mutants, PI3K acts independently of RTK signaling, converting PIP2 to PIP3 leading to hyperactive downstream AKT, activating the signal pathway with no ligand present in the RTK. This hyperactivation leads to increased and unregulated cell proliferation and survival¹. This double mutant PIK3CA is a common mutations in many cancers, especially breast cancer.