Lecture 10
Gene Control in DevelopmentCell 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
MCM1 is a general transcription factor found in all cell types
Different mating types express specific transcription factors that form complexes with MCM1
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 animals
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
Development of an organism: Drosophila melanogaster
Drosophila has two life forms
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
Mechanisms controlling pattern formation
Morphogens regulate development as a function of their concentration: maternal bicoid
gene specifies anterior region in Drosophila
Yellow: even-skippedOrange: fushi tarazu
Red: hunchbackGreen: 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
Three classes of genes control floral-organ identity
Expression patterns of floral organ-identity genes
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