Developmental biology...............................................................................................................2
Chapter 4: cell-to-cell communication: 94-96 & 100-113......................................................2
The epithelial-mesenchymal transition..............................................................................2
Cell signaling........................................................................................................................2
Paracrine factors: inducer molecules.................................................................................3
Further development 4.8: Downstream Events of the FGF Signal Transduction Cascade. 8
Further development 4.10: FGF Receptor Mutations........................................................9
Chapter 6: sex determination and gametogenesis: 159-169 & 174-183..............................10
Sexual reproduction is the masterpiece of nature...........................................................10
Chromosomal sex determination.....................................................................................11
The mammalian pattern of sex determination.................................................................11
Gametogenesis in Animals................................................................................................15
Further development 6.2..................................................................................................18
Further development 6.3..................................................................................................18
Further development 6.4..................................................................................................18
Further development 6.5..................................................................................................18
Further development 6.6..................................................................................................18
Further development 6.7..................................................................................................18
Further development 6.8..................................................................................................18
Further development 6.9..................................................................................................18
Chapter 12: birds and mammals...........................................................................................18
Early development in mammals.......................................................................................18
Further development 12.12: Anterior-Posterior Patterning by FGF and RA Gradients. . .23
Further development 12.13: Experimental Analysis of the Hox Code.............................23
Chapter 13: neural tube formation and patterning..............................................................23
Transforming the neural plate into a tube: the birth of the central nervous system......24
Patterning the CNS............................................................................................................26
All axes come together.....................................................................................................27
Chapter 15: neural crest cells and axonal specificity............................................................28
Regionalization of the neural crest...................................................................................28
Neural crest: multipotent stem cells?...............................................................................29
Migration pathways of trunk neural crest cells................................................................29
Chapter 17: paraxial mesoderm: the somites and their derivatives....................................30
,Developmental biology
Chapter 4: cell-to-cell communication: 94-96 & 100-113
The epithelial-mesenchymal transition
Epithelial-mesenchymal transition (EMT) is a series of events whereby epithelial cells are
transformed into mesenchymal cells. In this transition, a polarized stationary epithelial cell,
which normally interacts with basal lamina through basal surface, becomes a migratory
mesenchymal cell that can invade tissues and help form organs in new places. EMT is usually
initiated when paracrine factors from neighboring cells alter gene expression in target cells
that change or downregulate their expression of cadherins, releasing their attachments to
other cells, or of integrins, releasing their attachment to components of the basal lamina.
This is accompanied by the secretion of enzymes that break down the basal lamina, allowing
the target cells to escape from the epithelium. These changes also often involve
rearrangements to the target cells’ actin cytoskeleton and the secretion of new extracellular
matrix molecules characteristic of mesenchymal cells.
EMT is critical during development. It occurs in
1. The formation of neural crest cells (neurale lijst cellen) from the dorsalmost region of
the neural tube
2. The formation of the mesoderm in chick embryos, wherein cells that had been part
of an epithelial layer become mesodermal and migrate into the embryo
3. The formation of vertebrae precursors from somites, wherein these cells detach from
the somite and migrate around the developing spinal cod
EMT is also needed in adults for wound healing and cancer metastasis: cells that have been
part of the tumor leave that tumor epithelium to invade other tissues as migratory
mesenchymal cells that form secondary tumors elsewhere: cadherins are downregulated,
the actin cytoskeleton is reorganized and the cells secrete enzymes such as
metalloproteinase to degrade the basal lamina while undergoing cell division.
Cell signaling
Induction and competence
When one group of cells communicate an organizing change in the behavior or
developmental trajectory of an adjacent set of cells = induction
Defining induction and competence
The first competent is the inducer: the tissue that produces a signal that changes the cellular
behavior of the other tissue. This signal is often a protein called a paracrine factor. Paracrine
factors are proteins made by a cell or a group of cells that alter the behavior or
differentiation of adjacent cells. Endocrine factors (hormones), travel through blood and
exert their effects on cells and tissues far away, paracrine factors are secreted into the
extracellular space and influence their close neighbors. The second component, the
responder, is the cell or tissue being induced. Cells of the responding tissue must have both
a receptor protein for the inducing factor and the ability to respond to the signal. The ability
to receive and respond to a specific inducer = competence.
, Paracrine factors: inducer molecules
When membrane proteins on one cell surface interact with receptor proteins on adjacent
cell surfaces = juxtacrine interaction. When proteins synthesized by one cell can diffuse over
a distance to induce changes in neighboring cells = paracrine interaction. Autocrine
interactions = the same cells that secrete the paracrine factors also respond to them: seen in
placental cytotrophoblast cells.
Morphogen gradients
One of the most important mechanisms governing cell fate specification involves gradients
of paracrine factors that regulate gene expression; such signaling molecules are called
morphogens. A morphogen = a diffusible biochemical molecule that can determine the fate
of a cell by its concentration: cells exposed to high levels of a morphogen activate different
genes than those cells exposed to lower levels. Morphogens can be transcription factors
(TFs) or paracrine factors. Uncommitted cells exposed to high concentrations of the
morphogen (nearest source of production) are specified as one cell type. When the
morphogen’s concentration drops below a certain threshold, a different cell fate is specified.
When the concentration falls even lower, a cell that initially was of the uncommitted type is
specified in a third distinct manner.
The range of a paracrine factor (and thus the shape of its morphogen gradient) depends on
several aspects of that factor’s synthesis, transport, and degradation. In some cases, cell
surface molecules stabilize the paracrine factor and aid in its diffusion, while in other cases,
cell surface moieties (a part or functional group of a molecule) retard diffusion and enhance
degradation. These diffusion-regulating interactions between morphogens and extracellular
matrix factors are very import in coordinating organ growth and shape.
Paracrine families
Many paracrine factors can be grouped into one of 4 major families on the basis of their
structure:
1. The fibroblast growth factor (FGF) family
2. The Hedgehog (HH) family
3. The Wingless (Wnt) family
4. The TGF-B superfamily, including the TGF-B family, the Activin family, the bone
morphogenetic proteins (BMPs), the Nodal proteins, the VG1 family and other
related proteins
Signal transduction cascades: the response to inducers
For a ligand to induce a cellular response in a cell, it must bind to a receptor, which starts a
cascade of events within the cell that ultimately regulates a response. This process = signal
transduction cascade. Paracrine factors work by binding to a receptor that initiates a series
of enzymatic reactions within the cell. These enzymatic reactions have as their end point
either the regulation of transcription factors (TFs) or the regulation of the cytoskeleton,
which lead to changes in gene expression or cell shape and movement, respectively.
The major signaling pathways all appear to be variations on a common and rather elegant
theme
Chapter 4: cell-to-cell communication: 94-96 & 100-113......................................................2
The epithelial-mesenchymal transition..............................................................................2
Cell signaling........................................................................................................................2
Paracrine factors: inducer molecules.................................................................................3
Further development 4.8: Downstream Events of the FGF Signal Transduction Cascade. 8
Further development 4.10: FGF Receptor Mutations........................................................9
Chapter 6: sex determination and gametogenesis: 159-169 & 174-183..............................10
Sexual reproduction is the masterpiece of nature...........................................................10
Chromosomal sex determination.....................................................................................11
The mammalian pattern of sex determination.................................................................11
Gametogenesis in Animals................................................................................................15
Further development 6.2..................................................................................................18
Further development 6.3..................................................................................................18
Further development 6.4..................................................................................................18
Further development 6.5..................................................................................................18
Further development 6.6..................................................................................................18
Further development 6.7..................................................................................................18
Further development 6.8..................................................................................................18
Further development 6.9..................................................................................................18
Chapter 12: birds and mammals...........................................................................................18
Early development in mammals.......................................................................................18
Further development 12.12: Anterior-Posterior Patterning by FGF and RA Gradients. . .23
Further development 12.13: Experimental Analysis of the Hox Code.............................23
Chapter 13: neural tube formation and patterning..............................................................23
Transforming the neural plate into a tube: the birth of the central nervous system......24
Patterning the CNS............................................................................................................26
All axes come together.....................................................................................................27
Chapter 15: neural crest cells and axonal specificity............................................................28
Regionalization of the neural crest...................................................................................28
Neural crest: multipotent stem cells?...............................................................................29
Migration pathways of trunk neural crest cells................................................................29
Chapter 17: paraxial mesoderm: the somites and their derivatives....................................30
,Developmental biology
Chapter 4: cell-to-cell communication: 94-96 & 100-113
The epithelial-mesenchymal transition
Epithelial-mesenchymal transition (EMT) is a series of events whereby epithelial cells are
transformed into mesenchymal cells. In this transition, a polarized stationary epithelial cell,
which normally interacts with basal lamina through basal surface, becomes a migratory
mesenchymal cell that can invade tissues and help form organs in new places. EMT is usually
initiated when paracrine factors from neighboring cells alter gene expression in target cells
that change or downregulate their expression of cadherins, releasing their attachments to
other cells, or of integrins, releasing their attachment to components of the basal lamina.
This is accompanied by the secretion of enzymes that break down the basal lamina, allowing
the target cells to escape from the epithelium. These changes also often involve
rearrangements to the target cells’ actin cytoskeleton and the secretion of new extracellular
matrix molecules characteristic of mesenchymal cells.
EMT is critical during development. It occurs in
1. The formation of neural crest cells (neurale lijst cellen) from the dorsalmost region of
the neural tube
2. The formation of the mesoderm in chick embryos, wherein cells that had been part
of an epithelial layer become mesodermal and migrate into the embryo
3. The formation of vertebrae precursors from somites, wherein these cells detach from
the somite and migrate around the developing spinal cod
EMT is also needed in adults for wound healing and cancer metastasis: cells that have been
part of the tumor leave that tumor epithelium to invade other tissues as migratory
mesenchymal cells that form secondary tumors elsewhere: cadherins are downregulated,
the actin cytoskeleton is reorganized and the cells secrete enzymes such as
metalloproteinase to degrade the basal lamina while undergoing cell division.
Cell signaling
Induction and competence
When one group of cells communicate an organizing change in the behavior or
developmental trajectory of an adjacent set of cells = induction
Defining induction and competence
The first competent is the inducer: the tissue that produces a signal that changes the cellular
behavior of the other tissue. This signal is often a protein called a paracrine factor. Paracrine
factors are proteins made by a cell or a group of cells that alter the behavior or
differentiation of adjacent cells. Endocrine factors (hormones), travel through blood and
exert their effects on cells and tissues far away, paracrine factors are secreted into the
extracellular space and influence their close neighbors. The second component, the
responder, is the cell or tissue being induced. Cells of the responding tissue must have both
a receptor protein for the inducing factor and the ability to respond to the signal. The ability
to receive and respond to a specific inducer = competence.
, Paracrine factors: inducer molecules
When membrane proteins on one cell surface interact with receptor proteins on adjacent
cell surfaces = juxtacrine interaction. When proteins synthesized by one cell can diffuse over
a distance to induce changes in neighboring cells = paracrine interaction. Autocrine
interactions = the same cells that secrete the paracrine factors also respond to them: seen in
placental cytotrophoblast cells.
Morphogen gradients
One of the most important mechanisms governing cell fate specification involves gradients
of paracrine factors that regulate gene expression; such signaling molecules are called
morphogens. A morphogen = a diffusible biochemical molecule that can determine the fate
of a cell by its concentration: cells exposed to high levels of a morphogen activate different
genes than those cells exposed to lower levels. Morphogens can be transcription factors
(TFs) or paracrine factors. Uncommitted cells exposed to high concentrations of the
morphogen (nearest source of production) are specified as one cell type. When the
morphogen’s concentration drops below a certain threshold, a different cell fate is specified.
When the concentration falls even lower, a cell that initially was of the uncommitted type is
specified in a third distinct manner.
The range of a paracrine factor (and thus the shape of its morphogen gradient) depends on
several aspects of that factor’s synthesis, transport, and degradation. In some cases, cell
surface molecules stabilize the paracrine factor and aid in its diffusion, while in other cases,
cell surface moieties (a part or functional group of a molecule) retard diffusion and enhance
degradation. These diffusion-regulating interactions between morphogens and extracellular
matrix factors are very import in coordinating organ growth and shape.
Paracrine families
Many paracrine factors can be grouped into one of 4 major families on the basis of their
structure:
1. The fibroblast growth factor (FGF) family
2. The Hedgehog (HH) family
3. The Wingless (Wnt) family
4. The TGF-B superfamily, including the TGF-B family, the Activin family, the bone
morphogenetic proteins (BMPs), the Nodal proteins, the VG1 family and other
related proteins
Signal transduction cascades: the response to inducers
For a ligand to induce a cellular response in a cell, it must bind to a receptor, which starts a
cascade of events within the cell that ultimately regulates a response. This process = signal
transduction cascade. Paracrine factors work by binding to a receptor that initiates a series
of enzymatic reactions within the cell. These enzymatic reactions have as their end point
either the regulation of transcription factors (TFs) or the regulation of the cytoskeleton,
which lead to changes in gene expression or cell shape and movement, respectively.
The major signaling pathways all appear to be variations on a common and rather elegant
theme
