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