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Bone development and skeletal growth Przemko Tylzanowski [email protected]

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Page 1: Bone development and skeletal growth · Wild type SHH expression in ZPA ZRS LMBRI Intron 5 DLX6 DLX5 SHH Mutant Ectopic SHH expression ZRS LMBRI Gain-of-function mutation DLX6 DLX5

Bone developmentand

skeletal growth

Przemko Tylzanowski

[email protected]

Page 2: Bone development and skeletal growth · Wild type SHH expression in ZPA ZRS LMBRI Intron 5 DLX6 DLX5 SHH Mutant Ectopic SHH expression ZRS LMBRI Gain-of-function mutation DLX6 DLX5

http://tolweb.org/tree/

Page 3: Bone development and skeletal growth · Wild type SHH expression in ZPA ZRS LMBRI Intron 5 DLX6 DLX5 SHH Mutant Ectopic SHH expression ZRS LMBRI Gain-of-function mutation DLX6 DLX5

http://www.hps.cam.ac.uk/people/hopwood/haeckel.pdf

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Page 5: Bone development and skeletal growth · Wild type SHH expression in ZPA ZRS LMBRI Intron 5 DLX6 DLX5 SHH Mutant Ectopic SHH expression ZRS LMBRI Gain-of-function mutation DLX6 DLX5

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Page 10: Bone development and skeletal growth · Wild type SHH expression in ZPA ZRS LMBRI Intron 5 DLX6 DLX5 SHH Mutant Ectopic SHH expression ZRS LMBRI Gain-of-function mutation DLX6 DLX5
Page 11: Bone development and skeletal growth · Wild type SHH expression in ZPA ZRS LMBRI Intron 5 DLX6 DLX5 SHH Mutant Ectopic SHH expression ZRS LMBRI Gain-of-function mutation DLX6 DLX5
Page 12: Bone development and skeletal growth · Wild type SHH expression in ZPA ZRS LMBRI Intron 5 DLX6 DLX5 SHH Mutant Ectopic SHH expression ZRS LMBRI Gain-of-function mutation DLX6 DLX5
Page 13: Bone development and skeletal growth · Wild type SHH expression in ZPA ZRS LMBRI Intron 5 DLX6 DLX5 SHH Mutant Ectopic SHH expression ZRS LMBRI Gain-of-function mutation DLX6 DLX5
Page 14: Bone development and skeletal growth · Wild type SHH expression in ZPA ZRS LMBRI Intron 5 DLX6 DLX5 SHH Mutant Ectopic SHH expression ZRS LMBRI Gain-of-function mutation DLX6 DLX5

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Collagen type II reporter

Page 15: Bone development and skeletal growth · Wild type SHH expression in ZPA ZRS LMBRI Intron 5 DLX6 DLX5 SHH Mutant Ectopic SHH expression ZRS LMBRI Gain-of-function mutation DLX6 DLX5
Page 16: Bone development and skeletal growth · Wild type SHH expression in ZPA ZRS LMBRI Intron 5 DLX6 DLX5 SHH Mutant Ectopic SHH expression ZRS LMBRI Gain-of-function mutation DLX6 DLX5

Weismann et al. Genetics 2015

Page 17: Bone development and skeletal growth · Wild type SHH expression in ZPA ZRS LMBRI Intron 5 DLX6 DLX5 SHH Mutant Ectopic SHH expression ZRS LMBRI Gain-of-function mutation DLX6 DLX5
Page 18: Bone development and skeletal growth · Wild type SHH expression in ZPA ZRS LMBRI Intron 5 DLX6 DLX5 SHH Mutant Ectopic SHH expression ZRS LMBRI Gain-of-function mutation DLX6 DLX5

http://www.scientificamerican.com/slideshow/neurology-neural-cells-brain-in-psychedelic-relief/#9

Livet et al., Nature 2007

http://www.scientificamerican.com/slideshow/neurology-neural-cells-brain-in-psychedelic-relief/#9
Page 19: Bone development and skeletal growth · Wild type SHH expression in ZPA ZRS LMBRI Intron 5 DLX6 DLX5 SHH Mutant Ectopic SHH expression ZRS LMBRI Gain-of-function mutation DLX6 DLX5

Histology

http://www.eurogrow.net/eug/Project+Information/Objectives

Page 20: Bone development and skeletal growth · Wild type SHH expression in ZPA ZRS LMBRI Intron 5 DLX6 DLX5 SHH Mutant Ectopic SHH expression ZRS LMBRI Gain-of-function mutation DLX6 DLX5

Li et al., eLife 2017

Page 21: Bone development and skeletal growth · Wild type SHH expression in ZPA ZRS LMBRI Intron 5 DLX6 DLX5 SHH Mutant Ectopic SHH expression ZRS LMBRI Gain-of-function mutation DLX6 DLX5
Page 22: Bone development and skeletal growth · Wild type SHH expression in ZPA ZRS LMBRI Intron 5 DLX6 DLX5 SHH Mutant Ectopic SHH expression ZRS LMBRI Gain-of-function mutation DLX6 DLX5

Li et al., FASEB J 2017

Page 23: Bone development and skeletal growth · Wild type SHH expression in ZPA ZRS LMBRI Intron 5 DLX6 DLX5 SHH Mutant Ectopic SHH expression ZRS LMBRI Gain-of-function mutation DLX6 DLX5
Page 24: Bone development and skeletal growth · Wild type SHH expression in ZPA ZRS LMBRI Intron 5 DLX6 DLX5 SHH Mutant Ectopic SHH expression ZRS LMBRI Gain-of-function mutation DLX6 DLX5

http://pixgood.com/lateral-plate-mesoderm.html

Page 25: Bone development and skeletal growth · Wild type SHH expression in ZPA ZRS LMBRI Intron 5 DLX6 DLX5 SHH Mutant Ectopic SHH expression ZRS LMBRI Gain-of-function mutation DLX6 DLX5

wt heterozygote

Human heterozygote

Human mutations in RUNX2 lead to cleidocranial dysplasia (CCD)

Otto et al. Cell, 1997 Mundlos et al. Cell, 1997

Page 26: Bone development and skeletal growth · Wild type SHH expression in ZPA ZRS LMBRI Intron 5 DLX6 DLX5 SHH Mutant Ectopic SHH expression ZRS LMBRI Gain-of-function mutation DLX6 DLX5
Page 27: Bone development and skeletal growth · Wild type SHH expression in ZPA ZRS LMBRI Intron 5 DLX6 DLX5 SHH Mutant Ectopic SHH expression ZRS LMBRI Gain-of-function mutation DLX6 DLX5

27Ingo Arndt

Page 28: Bone development and skeletal growth · Wild type SHH expression in ZPA ZRS LMBRI Intron 5 DLX6 DLX5 SHH Mutant Ectopic SHH expression ZRS LMBRI Gain-of-function mutation DLX6 DLX5

Spielman et al. HMG 2016

Page 29: Bone development and skeletal growth · Wild type SHH expression in ZPA ZRS LMBRI Intron 5 DLX6 DLX5 SHH Mutant Ectopic SHH expression ZRS LMBRI Gain-of-function mutation DLX6 DLX5
Page 30: Bone development and skeletal growth · Wild type SHH expression in ZPA ZRS LMBRI Intron 5 DLX6 DLX5 SHH Mutant Ectopic SHH expression ZRS LMBRI Gain-of-function mutation DLX6 DLX5

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Page 31: Bone development and skeletal growth · Wild type SHH expression in ZPA ZRS LMBRI Intron 5 DLX6 DLX5 SHH Mutant Ectopic SHH expression ZRS LMBRI Gain-of-function mutation DLX6 DLX5

Lupianez et al, Cell 2015

Page 32: Bone development and skeletal growth · Wild type SHH expression in ZPA ZRS LMBRI Intron 5 DLX6 DLX5 SHH Mutant Ectopic SHH expression ZRS LMBRI Gain-of-function mutation DLX6 DLX5

Petit et al., NatRevGen 2017

Page 33: Bone development and skeletal growth · Wild type SHH expression in ZPA ZRS LMBRI Intron 5 DLX6 DLX5 SHH Mutant Ectopic SHH expression ZRS LMBRI Gain-of-function mutation DLX6 DLX5
Page 34: Bone development and skeletal growth · Wild type SHH expression in ZPA ZRS LMBRI Intron 5 DLX6 DLX5 SHH Mutant Ectopic SHH expression ZRS LMBRI Gain-of-function mutation DLX6 DLX5

Spielman et al. AJHG 2012

Liebenberg Syndrome

Page 35: Bone development and skeletal growth · Wild type SHH expression in ZPA ZRS LMBRI Intron 5 DLX6 DLX5 SHH Mutant Ectopic SHH expression ZRS LMBRI Gain-of-function mutation DLX6 DLX5
Page 36: Bone development and skeletal growth · Wild type SHH expression in ZPA ZRS LMBRI Intron 5 DLX6 DLX5 SHH Mutant Ectopic SHH expression ZRS LMBRI Gain-of-function mutation DLX6 DLX5
Page 37: Bone development and skeletal growth · Wild type SHH expression in ZPA ZRS LMBRI Intron 5 DLX6 DLX5 SHH Mutant Ectopic SHH expression ZRS LMBRI Gain-of-function mutation DLX6 DLX5

Ospelt et al, NatRevRheuma. 2017

Page 38: Bone development and skeletal growth · Wild type SHH expression in ZPA ZRS LMBRI Intron 5 DLX6 DLX5 SHH Mutant Ectopic SHH expression ZRS LMBRI Gain-of-function mutation DLX6 DLX5

Thank you


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