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Lecture 10 Gene Control in Development Cell type specification Development of an organism Reading: Chapter 11:471-2 Chapter 15.1; 15.3; 15.4 Chapter 22.2. Molecular Biology syllabus web site. Cell type specification in the yeast model system.
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Lecture 10 Gene Control in Development Cell type specification Development of an organism Reading: Chapter 11:471-2 Chapter 15.1; 15.3; 15.4 Chapter 22.2 Molecular Biology syllabus web site
Different mating types express specific transcription factors that form complexes with MCM1 MCM1 is a general transcription factor found in all cell types
Transcription factors and lessons from yeast • Factors may act alone or in combinations • The same factor in different combinations may contribute to complexes that act as repressors or activators.
Cell type specification in mammals: skeletal myogenesis proceeds through three stages
How to identify factors involved in muscle development? To identify transcription factors that may play a role in “determination” of cells destined for a specific organ: • Isolation of cDNAs by subtractive hybridization (fibroblasts vs. myoblasts) • Testing by transformation of undetermined cell types to demonstrate effect on “determination” • Create “Knockouts” to confirm information on the stage at which a specific factor acts • Characterization: function as heterodimers (key to specificity is the interaction with other factors) and belong to family of basic helix-loop-helix DNA binding transcription factors (bHLH) MRFs, muscle regulatory factors binding to “E” box in many genes
Microarray analysis shows global patterns of gene expression during differentiation
Patterning information is generated during oogenesis and early embryogenesis
Formation of the blastula during Drosophila early embryogenesis
Four maternal gene systems (anterior, posterior, terminal, dorsoventral) control early patterning in fly embryos
Morphogens regulate development as a function of their concentration: maternal bicoid gene specifies anterior region in Drosophila Yellow: even-skipped Orange: fushi tarazu Red: hunchback Green: Krupple
Maternally derived inhibitors of translation contribute to early Drosophila patterning
Nanos regulates the translation of Hunchback and helps to establish the Hunchback gradient
Use of mutants to characterize Nanos as a translational inhibitor
HOX genes and transcription factors discovered through “homeotic mutants” showing transformation of one body part into another
Expression domains of Hox genes in Drosophila and mouse embryos
Specification of floral-organ identity in Arabidopsis: flowers contain four different organs