2008-Shanghai-Beijing-lectures-2.pptVIP

15_09 15_11 * comp.uark.edu/~mlehmann/post.pdf Hierarchy of gene actions during embryonic development Wilt Hake, 2004 Cuticle/larva Embryo S. F. Gilbert, 2000 Wilt Hake, 2004 Genes controlling anterior-posterior patterning in Drosophila Ephrussi St Johnston, 2004 First morphogenetic protein identified (sufficient for induction: injection experiments) Biologically relevant target genes are known (implications in signaling) Concentration-dependent activator (and translation repressor) Precision of target gene expression Implications in understanding diseases (e.g., PITX2) Bicoid as a molecular morphogen instructing embryonic patterning Driever et al., 1990 Injection of bicoid mRNA is sufficient to induce head structures Ephrussi St Johnston, 2004 Localization of bicoid mRNA at the anterior of the egg Syncytial Drosophila embryos Wilt Hake, 2004 Threshold responses to the Bcd gradient GTF recruitment Co-factor function Chromatin involvement On/off switch (morphogen property #1) Distinct responses (property #2) Precise and reproducible outputs (property #3) Threshold action of Bcd: cooperative DNA binding to enhancers Ma et al. (1996) Development 122, 1195-1206 Direct interaction between Bcd molecules Enhancer-specific domains in cooperativity Specific patterns of DNA sites preferred by Bcd Wilt Hake, 2004 Pair-rule gene expression patterns in embryos Distinct enhancer elements controlling even-skipped expression stripes Howard Davidson, 2004 Wilt Hake, 2004 Homeotic genes control segment identity Flybase wt Antp Conservation and colinearity of homeotic genes S. Potter, Chapter 18, Gene Expression and Regulation, 2006 Bicoid homeodomain structure A self-inhibitory domain of Bicoid Cooperative DNA binding by Bicoid Co-factor interactions: Sin3A, dCBP PFDLLFDERTGAINYNYIRPYLPNQMPKPEELPDSLVMRR 4EHP (eIF4E homologous protein) (translation repression) Co-repressor(s) (self-inhibition) Cooperativity (kni enhancer) Competing factor(s)? DNA RNA binding Transcri