Reflections: Tetra-Amelia

Last week in our Developmental Biology class, we did presentations on different topics. I did my presentation on Tetra-Amelia. Tetra-Amelia is an autosomal recessive disorder that has the phenotypic results of absence of all four limbs. Tetra-Amelia causes severe malformations in the face, head, heart, nervous system,skeleton, genitalia and lungs. It is caused by a mutatio on the WNT3 gene.
In class we studied the WNT pathway. The WNT genes play a critical role in development before birth. It gives instructions to make proteins that will be a part of the WNT chemical signaling pathway. The WNT3 gene is specific to creating certain genes that are responsible for the development of limbs.

The WNT proteins are ligands and are able to bidn to receptors on other proteins. They bind to the receptor frizzled protein. This binding to frizzled causes the activation of the disheveled protein. Disheveled then inhibits glycogen synthase kinase 3 (GSK3). When GSK3 is inactive, B-catenin is free to associate with an LEF or TCF protein. This association with the two proteins acts like and becomes a transcription factor. These cascade of effects causes growth and division of cells that will later determine what those cells will differentiate into. The WNT3 gene is critical for outgrowth of limbs and is critical for determining the anterior-posterior axis. IT has five exons and encodes for a protein that has 355 amino acids. When the sequence of WNT3 was done, a nonsense mutation was found. The nonsense mutation at codon 83 created a premature stop codon. This causes only 82 amino acids to be produced instead of 355 amino acids

Dictionary: Cell Signaling

How do cells know where to go and how do they communicate with each other? This process is done by induction, which is an interaction between tissues and or cells within close proximity of each other. Induction has two steps, the inducer (what produces the signal) and the responder (the tissue or cell being induced). In order for the cell to respond to the inducer, must be able to respond to the signal. This ability to respond to a signal is called competence. Each cell has a receptor for the signaling pathways. There are four types of ways cells signal each other.

1. Autocrine --> affecting itself
2. Paracrine --> adjacent to each other
1. FGF
2. Hedgehog
3. WNT
4. TGF-B
3. Juxtacrine --> no diffusion; adjacent to each other (CONTACT)
4. Endocrine --> far from each other
1. Ex: Hormones

Together these different signals work together in development processes. If there is a mutation in a receptor, then the correct protein will not produced or may not be produced at all. This can cause many developmental issues in the organism.

Encounters: Zebrafish

Unfortunately, our zebrafish did not lay any eggs, so we were not able to observe the development of the zebrafish. I was very interested to see the development of the zebrafish, since their embryos are see through. I went online and found a youtube video of the developmental stages from zygote to the larval period.

The stages of the zebrafish development begins with the zygote period, in which the zygote reaches its morula stage and then reaches the 2 cell stage.

 

Within about 0.75 to 2.25 hours, it reaches the cleveage period where it will divide into the 64 cell stage. Meroblastic cleavage occurs in the zebrafish.

Between 2.25 and 5.25 hours, the embryo reaches the blastula stage. After the mid-blastula transition stage

Gastrulation begins between 5.25 10.33 hours. The tailbud begins to form and 2 somites can be observed.

Betwen 10.33 and 24 hours, segmentation begins to happen. This the period in which the folding of the embryo begins to occur and the formation of the somites begins to continue. The embryo begins to elongate and the neural cord and notochord continue to develop. During this stage, the dermis, vertebrae and skeletal muscle are formed as well.

The next stage that happens is the pharyngula period, which occurs between 24-48 hours. During this time period, the notochord is fully developed, the pectoral fins begin development and the cirgulatory system can be observed along with a heart beat.



The next step is the hatching period in which the olfactor palcodes are fully developed, the pectoral fins are elongated and the development of cartilage begins. This stage usually occurs between 48 and 72 hours.

The last stage of development of the zebrafish is the larval period.

VIDEO OF ZEBRAFISH DEVELOPMENT

Investigations: KG5

Thousands of people die from cancer each year. Those who survive still have a risk of the cancer returning again in later years. There might just be hope for those with cancer thanks to the many time, energy, and dollars put into finidng a cure or better treatment. Researchers from University of San Diego created a drug that is able to change the shape of the protein RAF. RAF is a protein that regulates cell proliferation and survival in normal cells, but in tumor cells, its regulation becomes irregular. The KG5 drug has only been tested on animals and tissue samples from patients with cancer. This drug is very primitive and scientists are hoping that they can use it for cancers that are invasive and have developed resistance to treatment.