Evo-Devo: The merging of Evolutionary and Developmental Biology Eddy M. De Robertis HHMI/UCLA, USA 1)Cell differentiation self-regulates during animal development. 2) Conserved ancestral gene networks control development of the Antero-Posterior (A-P) and Dorso-Ventral (D-V) embryonic axes. 3) Evolution has been channeled by an ancestral “primeval genome” tool-kit shared by all animals. Slide 1

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The early embryo is a self-regulating field In 1901 Hans Spemann used baby hair ligature to induce twins Slide 3

Self-regulating morphogenetic fields: Ross Harrison, 1918 Ross Harrison Slide 4

The Organizer experiment Slide 5

The discovery of embryonic induction represented the apogee of developmental biology, for which Spemann received the Nobel Prize in After that, the genetics of Thomas H. Morgan became the pre- eminent science for the most of the 20 th century. Embryonic induction: tissue differentiations are directed by neighboring cells Slide 6

Thomas H. Morgan Bithorax, a four-winged Drosophila mutant. Bridges and Morgan, 1923 Slide 7

Homeotic genes specify A-P segment identity in Drosophila. Colinearity between their order in DNA and in the body. Edward B. Lewis Slide 8

Walter Gehring Matthew Scott “A Xenopus laevis gene was cloned on the basis of cross-homology to a region conserved between several Drosophila homeotic genes… This gene could perhaps represent the first development- controlling gene identified in vertebrates.” Carrasco, McGinnis, Gehring and De Robertis, Cell 1984 Homeobox DNA encodes a DNA-binding protein domain of 60 amino acids called the Homeodomain. Slide 9

Hox complexes are conserved between Drosophila and mammals (from De Robertis, Oliver and Wright, Scientific American, 1990) Slide 10

Evo-Devo: the A-P Hox patterning system was conserved Hox-C6, the first vertebrate Hox gene cloned. De Robertis, Cell 2008 Slide 11

De Robertis & Sasai, Nature 1996 Evo-Devo: the common urbilaterian ancestor had a Hox complex with least seven Hox genes. Ur = Primeval Bilateria = all bilateral animals (30 phyla) Slide 12

F. Jacob In October 1991, a meeting on “Evolution and Development” was held in Crete in honor of F. Jacob's retirement Slide 13

S. J. Gould Etienne Geoffroy Saint-Hilaire’s lobster Slide 14

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Chordin is a BMP antagonist required for Spemann organizer function BMP = Bone Morphogenetic Protein Slide 16

Chordin/BMP pathway: a network of interacting extracellular proteins BMP4 Slide 17

De Robertis, Cell 2008 The Chordin/BMP network patterns D-V differentiation in vertebrates, Drosophila, and many other animals. Slide 18

Evo-Devo: Urbilateria used the Chordin/BMP/Tolloid pathway for D-V cell differentiations One common gene tool-kit Slide 19

Owl Coquille Saint-Jacques Sepia Insect Walter Gehring Slide 20

Expression of mouse Pax6 induces ectopic eyes in Drosophila Eyes evolved only once. Slide 21

Musca Hypothetical Mammalian retina Cajal and Sanchez, 1915 The ancestral eye was complex. Slide 22

Evo-Devo: Urbilateria had complex neural circuits One common gene tool-kit Slide 23

13 Wnts in humans 12 Wnt families in Sea Anemone 5 Wnts 7 Wnts Genomes contain the record of our evolutionary history Gene deletions were common during evolution Slide 24

Developmental control networks placed evolutionary constraints on the animal anatomies that evolved by natural selection Slide 25

Future directions in Evo-Devo: 1)Reconstruct the ancestral animal genomic tool-kit. 2)Retrace the genetic mutations, duplications and deletions that actually caused adaptations in the course of evolution. How has the obligatory use of ancient developmental gene networks channeled these outcomes? 3)Establish how cells integrate positional information within fields of cells to decide when to divide, differentiate or die. Slide 26

In sum, animals evolved through variations in ancestral gene networks hard-wired in our DNA. Slide 27