vertebrate anogenital development - musc of... · elaine dzierzak & nancy a speck. (2008)...
TRANSCRIPT
![Page 1: Vertebrate Anogenital Development - MUSC of... · Elaine Dzierzak & Nancy A Speck. (2008) Nature Immunology 9, 129 - 136 E7.5 E8.5 E9.5 E10.5](https://reader033.vdocuments.us/reader033/viewer/2022050103/5f41dcab671707126431df33/html5/thumbnails/1.jpg)
Vertebrate Anogenital Development
Ashley W. Seifert
Department of Biology
![Page 2: Vertebrate Anogenital Development - MUSC of... · Elaine Dzierzak & Nancy A Speck. (2008) Nature Immunology 9, 129 - 136 E7.5 E8.5 E9.5 E10.5](https://reader033.vdocuments.us/reader033/viewer/2022050103/5f41dcab671707126431df33/html5/thumbnails/2.jpg)
Murine External Genital Development
![Page 3: Vertebrate Anogenital Development - MUSC of... · Elaine Dzierzak & Nancy A Speck. (2008) Nature Immunology 9, 129 - 136 E7.5 E8.5 E9.5 E10.5](https://reader033.vdocuments.us/reader033/viewer/2022050103/5f41dcab671707126431df33/html5/thumbnails/3.jpg)
Penis of the deer mouse, Peromyscus maniculatus
from Hooper.! 1958.! Mus. Zool. Univ. Mich. Misc. Publ. 105.
![Page 4: Vertebrate Anogenital Development - MUSC of... · Elaine Dzierzak & Nancy A Speck. (2008) Nature Immunology 9, 129 - 136 E7.5 E8.5 E9.5 E10.5](https://reader033.vdocuments.us/reader033/viewer/2022050103/5f41dcab671707126431df33/html5/thumbnails/4.jpg)
Elaine Dzierzak & Nancy A Speck. (2008) Nature Immunology 9, 129 - 136
E9.5 E10.5E8.5E7.5
![Page 5: Vertebrate Anogenital Development - MUSC of... · Elaine Dzierzak & Nancy A Speck. (2008) Nature Immunology 9, 129 - 136 E7.5 E8.5 E9.5 E10.5](https://reader033.vdocuments.us/reader033/viewer/2022050103/5f41dcab671707126431df33/html5/thumbnails/5.jpg)
![Page 6: Vertebrate Anogenital Development - MUSC of... · Elaine Dzierzak & Nancy A Speck. (2008) Nature Immunology 9, 129 - 136 E7.5 E8.5 E9.5 E10.5](https://reader033.vdocuments.us/reader033/viewer/2022050103/5f41dcab671707126431df33/html5/thumbnails/6.jpg)
E10.5: germ cells are arriving
at the genital ridges and begin
to invade the gonad
![Page 7: Vertebrate Anogenital Development - MUSC of... · Elaine Dzierzak & Nancy A Speck. (2008) Nature Immunology 9, 129 - 136 E7.5 E8.5 E9.5 E10.5](https://reader033.vdocuments.us/reader033/viewer/2022050103/5f41dcab671707126431df33/html5/thumbnails/7.jpg)
![Page 8: Vertebrate Anogenital Development - MUSC of... · Elaine Dzierzak & Nancy A Speck. (2008) Nature Immunology 9, 129 - 136 E7.5 E8.5 E9.5 E10.5](https://reader033.vdocuments.us/reader033/viewer/2022050103/5f41dcab671707126431df33/html5/thumbnails/8.jpg)
External Genital
Development Begins
![Page 9: Vertebrate Anogenital Development - MUSC of... · Elaine Dzierzak & Nancy A Speck. (2008) Nature Immunology 9, 129 - 136 E7.5 E8.5 E9.5 E10.5](https://reader033.vdocuments.us/reader033/viewer/2022050103/5f41dcab671707126431df33/html5/thumbnails/9.jpg)
Male Female
![Page 10: Vertebrate Anogenital Development - MUSC of... · Elaine Dzierzak & Nancy A Speck. (2008) Nature Immunology 9, 129 - 136 E7.5 E8.5 E9.5 E10.5](https://reader033.vdocuments.us/reader033/viewer/2022050103/5f41dcab671707126431df33/html5/thumbnails/10.jpg)
Modified from: Perriton (2003) Dissertation
Male Female
urethra
urethra
prepuce
glans
![Page 11: Vertebrate Anogenital Development - MUSC of... · Elaine Dzierzak & Nancy A Speck. (2008) Nature Immunology 9, 129 - 136 E7.5 E8.5 E9.5 E10.5](https://reader033.vdocuments.us/reader033/viewer/2022050103/5f41dcab671707126431df33/html5/thumbnails/11.jpg)
Ectodermpreputial
glands, skin
Mesoderm
erectile tissue,
connective
tissue, smooth
muscle,
cartliage, bone
Endoderm
urethra
![Page 12: Vertebrate Anogenital Development - MUSC of... · Elaine Dzierzak & Nancy A Speck. (2008) Nature Immunology 9, 129 - 136 E7.5 E8.5 E9.5 E10.5](https://reader033.vdocuments.us/reader033/viewer/2022050103/5f41dcab671707126431df33/html5/thumbnails/12.jpg)
E9.5 E10.75 E11.5
E12.0 E12.5 E13.5
![Page 13: Vertebrate Anogenital Development - MUSC of... · Elaine Dzierzak & Nancy A Speck. (2008) Nature Immunology 9, 129 - 136 E7.5 E8.5 E9.5 E10.5](https://reader033.vdocuments.us/reader033/viewer/2022050103/5f41dcab671707126431df33/html5/thumbnails/13.jpg)
![Page 14: Vertebrate Anogenital Development - MUSC of... · Elaine Dzierzak & Nancy A Speck. (2008) Nature Immunology 9, 129 - 136 E7.5 E8.5 E9.5 E10.5](https://reader033.vdocuments.us/reader033/viewer/2022050103/5f41dcab671707126431df33/html5/thumbnails/14.jpg)
Seifert et al. 2008 Dev. Biol
Mouse E10.5 E11.0 E12.5 E13.5
tail tail tail
cloacalmembrane
hindgut
urogenitalsinus
genitaltubercle
![Page 15: Vertebrate Anogenital Development - MUSC of... · Elaine Dzierzak & Nancy A Speck. (2008) Nature Immunology 9, 129 - 136 E7.5 E8.5 E9.5 E10.5](https://reader033.vdocuments.us/reader033/viewer/2022050103/5f41dcab671707126431df33/html5/thumbnails/15.jpg)
Sexual Differentiation
E15.5
E14.5
Male Female
Seifert et al. 2008 Dev. BiolModified from: Perriton (2003) Dissertation
Hormonal Regulation
![Page 16: Vertebrate Anogenital Development - MUSC of... · Elaine Dzierzak & Nancy A Speck. (2008) Nature Immunology 9, 129 - 136 E7.5 E8.5 E9.5 E10.5](https://reader033.vdocuments.us/reader033/viewer/2022050103/5f41dcab671707126431df33/html5/thumbnails/16.jpg)
Male Female
![Page 17: Vertebrate Anogenital Development - MUSC of... · Elaine Dzierzak & Nancy A Speck. (2008) Nature Immunology 9, 129 - 136 E7.5 E8.5 E9.5 E10.5](https://reader033.vdocuments.us/reader033/viewer/2022050103/5f41dcab671707126431df33/html5/thumbnails/17.jpg)
Seifert et al. 2008 Dev. Biol
Androgen signaling drives masculinization
![Page 18: Vertebrate Anogenital Development - MUSC of... · Elaine Dzierzak & Nancy A Speck. (2008) Nature Immunology 9, 129 - 136 E7.5 E8.5 E9.5 E10.5](https://reader033.vdocuments.us/reader033/viewer/2022050103/5f41dcab671707126431df33/html5/thumbnails/18.jpg)
Sexual Maturation of the
External Genitalia
Human St. 22 (E52) = ~mouse E14.5
♂
♀
ADULT
ADULT
O'Rahilly and Müller 1987. The Carnegie Collection
SEM images courtesy of Kathy Sulik
+ Testosterone
![Page 19: Vertebrate Anogenital Development - MUSC of... · Elaine Dzierzak & Nancy A Speck. (2008) Nature Immunology 9, 129 - 136 E7.5 E8.5 E9.5 E10.5](https://reader033.vdocuments.us/reader033/viewer/2022050103/5f41dcab671707126431df33/html5/thumbnails/19.jpg)
Seifert et al. 2008 Dev. Biol
Androgen signaling drives masculinization
![Page 20: Vertebrate Anogenital Development - MUSC of... · Elaine Dzierzak & Nancy A Speck. (2008) Nature Immunology 9, 129 - 136 E7.5 E8.5 E9.5 E10.5](https://reader033.vdocuments.us/reader033/viewer/2022050103/5f41dcab671707126431df33/html5/thumbnails/20.jpg)
From morphology to molecules...
![Page 21: Vertebrate Anogenital Development - MUSC of... · Elaine Dzierzak & Nancy A Speck. (2008) Nature Immunology 9, 129 - 136 E7.5 E8.5 E9.5 E10.5](https://reader033.vdocuments.us/reader033/viewer/2022050103/5f41dcab671707126431df33/html5/thumbnails/21.jpg)
C1qA! Eya1! Msx2! Shh!
Twist! En-1! Fgf8! Wnt5a!
![Page 22: Vertebrate Anogenital Development - MUSC of... · Elaine Dzierzak & Nancy A Speck. (2008) Nature Immunology 9, 129 - 136 E7.5 E8.5 E9.5 E10.5](https://reader033.vdocuments.us/reader033/viewer/2022050103/5f41dcab671707126431df33/html5/thumbnails/22.jpg)
Sonic hedgehog expression
Modified from: Perriton (2003) Dissertation
![Page 23: Vertebrate Anogenital Development - MUSC of... · Elaine Dzierzak & Nancy A Speck. (2008) Nature Immunology 9, 129 - 136 E7.5 E8.5 E9.5 E10.5](https://reader033.vdocuments.us/reader033/viewer/2022050103/5f41dcab671707126431df33/html5/thumbnails/23.jpg)
Wildtype mouse Mouse null for Sonic hedgehog
![Page 24: Vertebrate Anogenital Development - MUSC of... · Elaine Dzierzak & Nancy A Speck. (2008) Nature Immunology 9, 129 - 136 E7.5 E8.5 E9.5 E10.5](https://reader033.vdocuments.us/reader033/viewer/2022050103/5f41dcab671707126431df33/html5/thumbnails/24.jpg)
Shh removed at various time points Wildtype
Seifert et al. (2009) Development
![Page 25: Vertebrate Anogenital Development - MUSC of... · Elaine Dzierzak & Nancy A Speck. (2008) Nature Immunology 9, 129 - 136 E7.5 E8.5 E9.5 E10.5](https://reader033.vdocuments.us/reader033/viewer/2022050103/5f41dcab671707126431df33/html5/thumbnails/25.jpg)
Seifert et al. (2009) Development
![Page 26: Vertebrate Anogenital Development - MUSC of... · Elaine Dzierzak & Nancy A Speck. (2008) Nature Immunology 9, 129 - 136 E7.5 E8.5 E9.5 E10.5](https://reader033.vdocuments.us/reader033/viewer/2022050103/5f41dcab671707126431df33/html5/thumbnails/26.jpg)
Abnormal Development: Research = Prevention
Some congenital malformations
affect multiple organ systems
and are infrequent
1:5000 up to 1:30,000
Del Campo et al. 1999 AMHG
Courtesy of Sarah Bowdoin M.D.
Baskin et al. 2001
Hypospadias
1:250 live births
![Page 27: Vertebrate Anogenital Development - MUSC of... · Elaine Dzierzak & Nancy A Speck. (2008) Nature Immunology 9, 129 - 136 E7.5 E8.5 E9.5 E10.5](https://reader033.vdocuments.us/reader033/viewer/2022050103/5f41dcab671707126431df33/html5/thumbnails/27.jpg)
Can investigate genetic networks during genital development
Perriton et al. (2004) Dev. Biol.
![Page 28: Vertebrate Anogenital Development - MUSC of... · Elaine Dzierzak & Nancy A Speck. (2008) Nature Immunology 9, 129 - 136 E7.5 E8.5 E9.5 E10.5](https://reader033.vdocuments.us/reader033/viewer/2022050103/5f41dcab671707126431df33/html5/thumbnails/28.jpg)
Andrea Feller and Blair Hedges. 1998. Molecular Phylogenetics and Evolution
external genitalia
(secondary loss)
??
![Page 29: Vertebrate Anogenital Development - MUSC of... · Elaine Dzierzak & Nancy A Speck. (2008) Nature Immunology 9, 129 - 136 E7.5 E8.5 E9.5 E10.5](https://reader033.vdocuments.us/reader033/viewer/2022050103/5f41dcab671707126431df33/html5/thumbnails/29.jpg)
Phenotypic Diversity in Morphological Structures
![Page 30: Vertebrate Anogenital Development - MUSC of... · Elaine Dzierzak & Nancy A Speck. (2008) Nature Immunology 9, 129 - 136 E7.5 E8.5 E9.5 E10.5](https://reader033.vdocuments.us/reader033/viewer/2022050103/5f41dcab671707126431df33/html5/thumbnails/30.jpg)
Photos: Michelle Leung (chick)
Classic model systems have no external genitalia
and undivided cloaca
![Page 31: Vertebrate Anogenital Development - MUSC of... · Elaine Dzierzak & Nancy A Speck. (2008) Nature Immunology 9, 129 - 136 E7.5 E8.5 E9.5 E10.5](https://reader033.vdocuments.us/reader033/viewer/2022050103/5f41dcab671707126431df33/html5/thumbnails/31.jpg)
turtle alligator duck
snake mouse
Modified from: Perriton (2003) Dissertation
![Page 32: Vertebrate Anogenital Development - MUSC of... · Elaine Dzierzak & Nancy A Speck. (2008) Nature Immunology 9, 129 - 136 E7.5 E8.5 E9.5 E10.5](https://reader033.vdocuments.us/reader033/viewer/2022050103/5f41dcab671707126431df33/html5/thumbnails/32.jpg)
Comparison of Shh expression in vertebrate genitalia
Modified from: Perriton (2003) Dissertation
turtle
duck
mouse