Posted by The topic of my project is how skeletal growth is hormonally regulated. A large part of what allows hormones to be regulated properly is primary cilia. Primary cilia are a type of cilia, organelles which project from the apical surface of cells and are largely responsible for transmitting signals. They are important in fluid motility and are critical for communication between cells, with special importance in early embryonic development (Ana et al., 2015). They are found in almost all cells in the human body. Ciliopathy’s are heterogeneous disorders which affect the development and function of primary cilia, resulting in a wide array of phenotypes for patients diagnosed with them (Epting et al., 2020). They can affect almost all types of tissues and organs, causing issues with the eyes, muscles, skeleton, peripheral and central nervous systems, etc. (Ana et al., 2015).
One rare ciliopathy is joubert syndrome, which is early onset and believed to be caused by the loss of certain genes which are important for encoding proteins essential for the development of primary cilia. It is characterized by mid and hind brain malformations, oculomotor apraxia, hypotonia, etc. (Epting et al., 2020). Because of the null mutation of these genes, patients’ primary cilia are often found to be longer than normal and in lesser numbers, increasing the likelihood of misinterpreted signals, leading to the issues in the development of a large number of structures.
One relatively common phenotype associated with Joubert syndrome is polydactyly, the development of additional phalanges. Joubert syndrome does not affect the diencephalon, the part of the brain containing the pituitary gland. The pituitary gland is responsible for secreting growth hormone (Lindsey and Mohan 2015). Because the primary cilia have been mutated, the transmission of ligands, such as hormones, have been disrupted from cell to cell. Growth hormone (GH) is a primary hormone involved in skeletal development, directly influencing bone formation by stimulating the production of insulin-like growth factor (IGF) (Lindsey and Mohan 2015). When the signals from growth hormone are relayed incorrectly, it can lead to disruptions in the production and release of IGF, causing patients to gain, lose, or experience functional problems with certain skeletal structures.
I decided to make a children’s book explaining the basics of ciliopathies, specifically joubert syndrome, because I have a six year old brother who was born with the disorder. I took the project as an opportunity to explore the disorder at a deeper level, focusing on finding a topic which could mesh into my pre-existing idea. I wanted to make a basic and easy to understand explanation for both his future use and for use by his peers and possibly teachers. Rather than focusing directly on the process in which hormones influence bone growth, my focus was on how cilia influence the hormones which then influence skeletal development. Although I possess absolutely no artistic talent, I hope I was able to depict things well enough to get the basic idea of his disorder across while also showing how hormones are able to directly influence the formation of bones.
bibliograhy
Anna, Erik de Vrieze, Alazami, A. M., Alzahrani, F., Malarkey, E. B., Nasrin Sorusch, Tebbe, L., Kuhns, S., Dam, van, Alhashem, A., Brahim Tabarki, Lu, Q., Lambacher, N. J., Kennedy, J., Bowie, R. V., Hetterschijt, L., Sylvia van Beersum, Jeroen van Reeuwijk, Boldt, K., & Kremer, H. (2015). KIAA0556 is a novel ciliary basal body component mutated in Joubert syndrome. Genome Biology, 16(1). https://doi.org/10.1186/s13059-015-0858-z
Epting, D., Senaratne, L. D. S., Ott, E., Holmgren, A., Sumathipala, D., Larsen, S. M., Wallmeier, J., Bracht, D., Frikstad, K.-A. M., Crowley, S., Sikiric, A., Barøy, T., Käsmann-Kellner, B., Decker, E., Decker, C., Bachmann, N., Patzke, S., Phelps, I. G., Katsanis, N., & Giles, R. (2020). Loss of CBY1 results in a ciliopathy characterized by features of Joubert syndrome. Human Mutation, 41(12), 2179–2194. https://doi.org/10.1002/humu.24127
Lindsey, Richard C., and Subburaman Mohan. “Skeletal Effects of Growth Hormone and Insulin-like Growth Factor-I Therapy.” Molecular and Cellular Endocrinology, vol. 432, no. 432, 5 Sept. 2016, pp. 44–55, www.ncbi.nlm.nih.gov/pmc/articles/PMC4808510/, https://doi.org/10.1016/j.mce.2015.09.017.
For some reason, no matter how i converted my images, files, embedded a link, etc. everything came up with an error. I tried for two hours to no avail, so as a last resort, i’m adding this URL. i made a Pinterest board containing the pages from my steam project. If you start at the first pin and swipe, you can read the pages in chronological order. I planned on using the cover to the book as the cover/featured image to this post, but it won’t even let me do that.