8/31/09!1!Biology 624 - Developmental Genetics!Lecture #2 – Models and Concepts!Developmental Behaviors During development, cells do the following:!--Divide!--Move!--Make adhesions with matrix and neighbors!--Change shape!--Differentiate***!--Activate and deactivate expression programs!Developmental Hierarchy 1. Specification 2. Determination 3. Differentiation The point when a cell will develop autonomously into a specific tissue or cell type in isolation."Specification!Field The total number of cells specified to form a specific cell type or tissue; i.e. all the cells of an embryo that have responded to an inducing signal. !Competence The ability of a group of cells to respond to an inducing signal.8/31/09!2!Determination The ability of a tissue to develop autonomously "irrespective of environment"Cell Fate The normal developmental pathway a cell, or group of cells, will undergo during embryogenesis. Specification vs. Competence vs. Fate Differentiation Elaboration of a single cell type that is often, but not always, fixed from that time onward Potency!The complete spectrum of cell types and tissues that a cell can develop into IF exposed to the proper micro-environment Pluripotent vs Totipotent Lineage!The developmental history or family tree reflecting the ancestry of a cell through out development!8/31/09!3!Model Systems!• Worm (Caenorhabditis elegans) C. elegans!• Fly (Drosophila melanogaster) Drosophila!• Fish (Danio rerio) Zebrafish!• Frog (Xenopus laevis and Xenopus tropicalis)!• Chick (Gallus gallus)!• Mouse (Mus Musculus domesticus)!Other Model Systems!• Slime Molds • Tunicates/Sea squirts/Ascidians • Sea urchin • Molluscs • Plants • Human 16h!0h! 6h!1.5h!cleavage!GASTRULATION!organogenesis!*!4.5d!24h!first cleavage!GASTRULATION!segmentation!*organogenesis!6.5d!20d!14d!implantation!4d!24h!cleavage!GASTRULATION!segmentation!*organogenesis!7d!21d!0h! 10h!2.5h! 24h!cleavage!GASTRULATION!organogenesis!*!dorsal closure!5h!2.8h!cleavage!GASTRULATION!segmentation!*organogenesis!24h!48-72h!10h!18h!3.5h!cleavage! GASTRULATION! neurulation!*organogenesis!36h!Caenorhabditis elegans Caenorhabditis elegans (3 Days)  Small number of cells! Simple anatomy! Few genes (approx. 2000)! Relatively fixed lineage -all relationships known ! Genetics and RNAi!C. elegans embryogenesis!16h!0h! 6h!1.5h!cleavage! GASTRULATION! organogenesis!*!8/31/09!4!Caenorhabditis elegans Hallmarks of Development! Self Fertilization (only males or hermaphrodites)! Fixed cell lineages! After hatching close resemblance to adult except lacks gonadal structures! 4 molts! Embryos transparent! Genetics and RNAi feeding! Drosophila melanogaster Drosophila melanogaster (12 Days)  Genetics! Mosaics! Polytene Chromosomes! Homologous Recombination!Drosophila embryogenesis!0h! 10h!2.5h! 24h!cleavage! GASTRULATION!organogenesis!*! dorsal closure! Drosophila melanogaster Hallmarks of Development! Develops as syncytium for first 9 divisions; i.e. molecules are free to diffuse across embryo.! Gastrulates at 3 hours! Germ band extension! Cells set aside after gastrulation as discrete units, Imaginal Discs, that will give rise to specific adult organs after morphogenesis! 3 molts! Develops as “upside down vertebrate”, e.g. nervous system on ventral portion of embryo, heart on ventral side! Drosophila melanogaster Hallmarks of Development! Develops as syncytium for first 9 divisions; i.e. molecules are free to diffuse across embryo.! Gastrulates at 3 hours! Germ band extension! Cells set aside after gastrulation as discrete units, Imaginal Discs, that will give rise to specific adult organs after morphogenesis! 3 molts! Develops as “upside down vertebrate”. Nervous system on ventral portion of embryo.!8/31/09!5! Drosophila melanogaster Drosophila melanogaster Drosophila melanogaster Hallmarks of Development! Develops as syncytium for first 9 divisions; i.e. molecules are free to diffuse across embryo.! Gastrulates at 3 hours! Germ band extension! Cells set aside after gastrulation as discrete units, Imaginal Discs, that will give rise to specific adult organs after morphogenesis! 3 molts! Develops as “upside down vertebrate”. Nervous system on ventral portion of embryo.! Drosophila melanogaster Xenopus laevis (Xenopus tropicalis) Frog embryogenesis!36h!18h!3.5h!cleavage! GASTRULATION! neurulation!*!organogenesis!8/31/09!6! Xenopus laevis (Xenopus tropicalis) Hallmarks of development! High Fecundity; large embryos! Early development under maternal control! No cell mixing! Good fate map via direct manipulation! Concepts of specification, determination etc.! Gastrulation well-studied! Explants (e.g. animal caps) can be cultured in !!simple salt solutions! MOs work well for gene knockdown!Metamorphosis Brachydanio rerio Brachydanio rerio (12 weeks)  Short life cycle! Transparent! High Fecundity! Relative ease of tissue transplantation! Genome has gone through a relatively !!recent duplication !Zebrafish embryogenesis!5h!2.8h!cleavage!GASTRULATION!segmentation!*!organogenesis!24h!48-72h!10h!Brachydanio rerio Hallmarks of development! High Fecundity! Embryos transparent and develop in sea water! Transgenesis; reporter lines; inducible gene expression; MOs! Development similar to frog but better genetics!8/31/09!7! Gallus gallus! Gallus gallus (3 months)! 100s of chromosomes; genetics poor! Generation time (fertilization to fertilization) long – up to a year; thus genetics poor! Historical (remember Aristotle!)!Chick embryogenesis!4d!24h!cleavage!GASTRULATION!segmentation!*! organogenesis!7d!21d!Egg laid! Gallus gallus!Hallmarks of development! Embryo develops outside mother (in ovo) and accessible for manipulations! Develops as a disc! Genes can be introduced by electroporation or retrovirus! Early development similar to mouse! Trace the fate of a group of cells in chick-quail chimera (or quail-mouse chimera)! Mus Musculus domesticus Mus Musculus domesticus (42 days)  Mammal! Genetics! ES cells! Homologous Recombination! Transgenics!8/31/09!8! Mus Musculus domesticus Hallmarks of development! Implants in