Download Biology 340 Molecular Biology

Biology 340 Molecular Biology
Lecture 25
Molecular Biology of Development
April 20, 2001
Reading: Chap. 14 pp. 553-563
Outline:
1. Differentiation and development
2. Major questions in developmental biology
To be covered by Joe Hammer and Sunloon Loh
3. Homeotic mutants of Drosophila (Joe)
4. Mouse homeotic genes: transgenics and knockouts (Sun)
Lecture:
1. How does a multicellular organism arise from a single cell?
Key processes involved:
--cell division (mitosis)
--differentiation: when daughter cells become new cell types able to carry out
new functions
Developmental biology: Study of the processes and changes occurring from
conception to adulthood in an organism.
2. Developmental questions being addressed using molecular biology
A. What genes are switched on or off in different cell types or tissues?
Example: Study of genes involved in the differentiation of somites (embryonic
cells destined to form muscle) into myoblasts (muscle cell precursors) and then
into myotubes (mature muscle cells).
--tissue specific transcription factors activate muscle gene expression,
including MyoD, Myf5, myogenin and MEFs.
B. How does a single-celled oocyte become an organism with a distinct
head and tail (anterior and posterior) and a back and front (dorsal and
ventral)?
Example: Early development in Drosophila.
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Key stages in Drosophila life cycle:
1. egg
2. larval stages (segmented worm)
3. pupae
4. adult (main segments: head, thorax and abdomen)
Body plan is laid down in early stages of development: (between egg and
hatching of first larval stage). See Figure 14-32 or CD-ROM animation
1. maternal proteins and mRNAs stored in oocyte determine earliest steps
2. different genes control development in different regions of the embryo
a. anterior--posterior genes (maternal bicoid mRNA localized to anterior end of
oocyte)
b. dorsal--ventral genes
3. gap genes (Hunchback, Krüppel and Knirps) are produced in the early zygote
and are expressed in "stripes" corresponding to different segments of the early
embryo
4. zygotic genes of several types specify the boundaries of the segments
a. pair-rule genes (Fushi tarazu and even-skipped) are expressed in alternating
odd or even segments
b. segment polarity genes (such as engrailed) determine the anterior, middle
and posterior of segments
c. selector genes determine the structures of body parts along the anterior and
posterior axis (homeotic mutants due to alteration of these types of genes)
C. What are the key molecules involved in development?
--most genes involved in development and differentiation encode transcription
factors that activate or repress transcription
Examples: bicoid, antennapedia--Homeobox (Hox genes)
--some genes involved in development and differentiation encode cell signaling
molecules (hormones or ligands) or their receptors
--morphogens are substances that determine cell identity as a function of their
concentration; transcription factors and diffusible ligands are morphogens
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