Transcript Intellectual Framework - City University of New York

Framework
• Developmental processes are driven by
differential gene expression
• Gene expression programs are induced by
signals between neighboring tissues of the
developing embryo
• Cell movements during embryogenesis
place particular tissues into juxtaposition
“Official glossary” (from Wolpert)
• Morphogen: Any substance active in pattern
formation whose spatial concentration varies
and to which cells respond differently at
different levels
• Morphogenesis: The process involved in
bringing about changes in form in the
developing embryo
• Pattern formation: Process by which cells in
a developing embryo acquire identities that
lead to a well-ordered spatial pattern of
activities
What development accomplishes
• Differentiation of all of the required celltypes from a single fertilized egg (oocyte)
• Morphogenesis: Precise arrangement of
these cells into tissues and organs
• Pattern formation: Precise arrangement of
tissues and organs to achieve a reproducibly
working organism capable of reproduction
• Epigenesis: the de novo formation of an
organism from “disordered” egg cytoplasm
Demonstration of nuclear
potential in Acetabularia (1930’s)
Figure 2.5
page 31
Gilbert
The nucleus and Epigenesis
• The nucleus contains the instructions that
drive epigenesis/development
• Chromatin is the instructional unit (DNA
plus proteins). The state of the chromatin is
set by “epigenetic control” mechanisms
• Covert “epigenetic” changes occur during
the early cleavages of the fertilized egg into
the blastomeres of the embryo
For example: DNA methylation
Embryonic cell division is not the
same in all kinds of organisms
Next slide
So there is a sense that these zygotes “know what
they are” when the begin to divide. The yolk and
its position obviously plays a role in determining
the cleavage pattern. But, there are sometimes
other products stored in the egg by the mother that
act as morphogenetic determinants.
Major morphogenetic strategies
• Autonomous specification
– Morphogenetic determinants deposited in the
egg become segregated by cell division
– Determination of cell fate is early
• Conditional specification
– Cell fate determination is later and depends on
the position of the blastomere in the embryo
– Removal of cells is compensated for by others
– Each cell has the potential to give rise to more
cells than it normally does
Pages 56-66 of text
Specification of cell fate:
Autonomous vs. Conditional
Syncitial specification
• Mainly seen in insects (Drosophila)
• Gradients form, over time, of morphogens
deposited in the egg by the mother
• These morphogens become segregated by
cell membranes which grow into the egg
• Drosophila lectures: End of February
GASTRULATION
• The process that puts cells into position to
have their fates determined
• Gastrulation involves a particular repertoire
of cell movements which can be classified
• Gastrulation will result in the formation of
three “germ layers” from which the organs
of the embryo will arise
Movements of Gastrulation
Result of gastrulation: The 3 germ layers
Gastrulation and Conditional
Specification
• Newly positioned tissues (germ layers)
interact with one another to “induce” organ
formation
– Cell-cell interactions via receptors (juxtacrine)
– Soluble signaling molecules (paracrine)
• Morphogen gradients link position to cell fate
• Signal transduction activates gene expression which
leads to specification and lineage commitment
Morphogen gradients: different concentrations
of a factor induce different gene expression
Stages of commitment to cell fate
• Specification
– Changes in gene expression which are labile
and changeable. The gene expression “allows”
that cell to differentiate along a pathway but
does not irreversibly commit the cell
• Determination
– Further changes in gene expression which seal
the lineage fate of the cell and eliminate
alternative choices
Pro-B cells from Pax-5 deficient mice are “specified”
IL-7
Im
l5
VpreB
B29
syk
btk
blk
lyn
Oct-2
E2A
PU.1
EBF
“Pro-B cell”
Pro-B cells from Pax-5 deficient mice are “specified”
but not “determined”
mouse
T cell
Im
l5
VpreB
B29
syk
btk
blk
lyn
“Pro-B cell”
Oct-2
E2A
PU.1
EBF
M-CSF
Macrophage
Trance
IL-2
Osteoclast
NK cell
GM-CSF
Dendritic
cell
Recent data illustrating the concepts
of specification vs. determination
Nutt, SL, et. al. (1999) Commitment to
the B-lymphoid lineage depends on
the transcription factor Pax-5
Nature, 401:556-562
B lymphocyte
development
E2A
EBF
specified
Pax-5
committed
Forming a solid organ
• How do cells “stick together” to form tissue?
• Coordination of tissues from multiple germ
layers to form a single functional organ
– Tissue layers
– Organ polarity
• Cell adhesion molecules: Cadherins (p66-74)
Cadherins (Ca2+dependent adhesion molecules)
See also
Website 3.8
Types of cadherins
• E- cadherin: expressed on early embryonic
cells in mammals. Later becomes restricted
to embryonic and adult epithelial tissue
• P-cadherin: Trophoblast cells (placental)
• N-cadherin: First mesodermal, later CNS
• EP-cadherin: frog blastomere adhesion
• Protocadherins: not connected to catenin
Mechanisms of cadherin based
cell “sorting” into tissues
• Differential expression of cadherin type
– Neural vs epidermal cells (N vs. E cadherin)
• Different levels of cadherin expression
– Oocyte positioning in follicle
• Loss or switch of cadherin expression
– Neural crest emigration from the neural tube
– Protocadherin switching in frog gastrulation
• See pages 311-312 (Chapter 10 of Gilbert)