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Transcript
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
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 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
Red: hunchback
Green: Krupple
Yellow: even-skipped
Orange: fushi tarazu
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 floralorgan identity
Expression patterns of floral organidentity genes