1. BMPR1A Bone Morphogenetic Protein Receptor 1 A (Juvenile Polyposis & Colon Cancer) Hallie Wieters

2. BMPR1A is part of a TGF-βReceptor Serine/Threonine Kinase

3. There are multiple ligands, receptors and many SMADs

4. BMPs can regulate cell differentiation, growth inhibition or apoptosis

5. KO BMPR1-A mutant mouse leads to embryonic lethality due to failed gastrulation

6. Continual loss of intestinal cells and repetitive cell cycle entry causes the colon to be prone to mutations

7. Juvenile Polyposis leads to colon polyp formation and thus a predisposition to colon cancer

8. Juvenile Polyposis is caused by germline mutations and loss of heterozygosity at BMPR1-A loci

9. Mutated BMPR1-A leads to increased proliferation, decreased differentiation, increased number of stem cells and cell persistence

10. Scientists have created a mouse model of juvenile polyposis by mutating BMPR1-A

11. Juvenile Polyposis can be diagnosed through genetic screening and treated through colon surveillance

12. Summary BMPR1A is a threonine/serine kinase receptor in the TGF- βfamily (growth-inhibitory  tumor suppressor) Germline Mutations cause a nonfunctional receptor leading to propagation of proliferating signals and an increase stem cells Inherited autosomal dominantly  recessive at the cellular level Lack of regulation in proliferation leads to development of polyps in the colon  Juvenile Polyposis

13. References He, X. C., Zhang, J., Tong, W.-G., Tawfik, O., Ross, J., Scoville, D. H., Tian, Q., Zeng, X., He, X., Wiedemann, L. M., Mishina, Y., Li, L. BMP signaling inhibits intestinal stem cell self-renewal through suppression of Wnt-beta-catenin signaling. Nature Genet. 36: 1117-1121, 2004. Cichy, Wojciech, Beata Klincewicz, and Andrzej Plawski. “Juvenile Polyposis Syndrome.” Archives of Medical Science: AMS 10.3 (2014): 570–577. PMC. Web. 2 Mar. 2015. Mishina, Yuji,Suzuki, A., Ueno, N., Behringer, R. Bmpr encodes a type 1 bone morphogenetic protein receptor that is essentail for gastrulation during mouse embryogenesis. Genes & Development, 9 (1995): 3027-3037. Waite, Kristen, Eng, C., From developmental disorder to heritable cancer : It’s all in the TGF-B Family. Nature Reviews: Genetics. 4 (2003) : 763-772. Zhou, Xiao-Ping et al. “Germline Mutations in BMPR1A/ALK3 Cause a Subset of Cases of Juvenile Polyposis Syndrome and of Cowden and Bannayan-Riley-Ruvalcaba Syndromes.” American Journal of Human Genetics 69.4 (2001): 704–711. Print. Chen, Di, Mundy, G. “Bone Morphogenetic Proteins”. Growth Factors 22 (2004):233-241