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Division of Orthopaedics

Developmental Biology

The ectodermal basis of early limb bud morphogenesis and malformation

SickKids Principal Investigator: Dr. Sevan Hopyan

Funding: CIHR

The aim here is to identify new morphogenetic mechanisms that underlie formation and malformation of the early limb bud.


  1. Lau K, Tao H, Liu H, Wen J, Sturgeon K, Sorfazlian N, Wong MD, Lazic S, Li D, Deimling S, Scott I, Simmons C, Henkelman RM, Williams T, Hadjantonakis K, Fernandez-Gonzalez R, Sun Y, Hopyan S. Anisotropic stress orients remodelling of mammalian limb bud ectoderm. In revision.
  2. Hopyan S, Sharpe J, Yang Y. Budding behaviors: Growth of the limb as a model of morphogenesis. Dev Dyn. 2011 May;240(5):1054-62. doi: 10.1002/dvdy.22601. Epub 2011 Mar 7. Review. PMID: 21384474. See publication.
  3. Wyngaarden LA, Vogeli KM, Ciruna BG, Wells M, Hadjantonakis AK, Hopyan S. Oriented cell motility and division underlie early limb bud morphogenesis. Development. 2010 Aug 1;137(15):2551-8. doi: 10.1242/dev.046987. Epub 2010 Jun 16. PMID: 20554720. See publication.

Genetic control of mammalian limb pattern

Principal Investigators: Dr. Sevan Hopyan & Dr. Chi-chung Hui

Funding: CIHR

The goal here is to define early genetic regulation of limb pattern and the basis for profound congenital deficiencies.


  1. Zhulyn O, Li D, Deimling S, Vakili NA, Mo R, Puviindran V, Chen MH, Chuang PT, Hopyan S, Hui CC. A switch from low to high Shh activity regulates establishment of limb progenitors and signaling centers. Dev Cell. 2014 Apr 28;29(2):241-9. doi: 10.1016/j.devcel.2014.03.002. Epub 2014 Apr 10. PMID:  24726283. See publication.
  2. Li D, Sakuma R, Vakili NA, Mo R, Puviindran V, Deimling S, Zhang X, Hopyan S, Hui CC. Formation of proximal and anterior limb skeleton requires early function of Irx3 and Irx5 and is negatively regulated by Shh signalling. Dev Cell. 2014 Apr 28;29(2):233-40. doi: 10.1016/j.devcel.2014.03.001. Epub 2014 Apr 10.  PMID: 24726282.  See publication.

FGFR3 in Skeletal Development and Repair

SickKids Principal Investigator: Dr. Simon Kelley

Funding: Institute of Medical Science, University of Toronto and Perioperative Services, The Hospital for Sick Children, Toronto

An abnormality of the FGFR3 gene causes achondroplasia, the most common of a group of genetic bone diseases called skeletal dysplasias. This laboratory based study investigates why stem cells with the FGFR3 mutation make bone and cartilage differently from normal cells.