H11: BRANCHING MORPHOGENESIS
P. CALLAERTS
INHOUDSOPGAVE
11. 1 BRANCHED STRUCTURES: WHERE AND WHY? ...................................................................................................... 2
11.2 BRANCHED STRUCTURES: FUNCTION AND STRUCTURE ........................................................................................ 2
11.3 BRANCHING MORPHOGENESIS: DEFINITION ......................................................................................................... 3
11.4 BRANCHING MORPHOGENESIS: STUDIED USING COMBINATION OF APPROACHES .............................................. 3
11.5 BRANCHING MORPHOGENESIS: MODES OF BRANCHING ...................................................................................... 3
11.6 BRANCHING MORPHOGENESIS: EVENTS AND REGULATION ................................................................................. 4
11.7 5 CASES ................................................................................................................................................................. 4
11.7.1 VASCULATURE ............................................................................................................................................................ 4
11.7.1.1 Vasculogenesis and angiogenesis ................................................................................................................... 4
11.7.1.2 Stages of vasculature development ................................................................................................................ 5
11.7.1.3 Vasculature development: cellular and molecular basis ................................................................................. 5
11.7.2 TRACHEAL SYSTEM....................................................................................................................................................... 7
11.7.2.1 Different stages of tracheal development: embryogenesis ............................................................................ 7
11.7.2.2 Different stages of tracheal development: metamorphosis ........................................................................... 7
11.7.2.3 Tracheal development: cellular basis .............................................................................................................. 7
11.7.2.4 Tracheal development: genetics ..................................................................................................................... 8
11.7.2.5 Tracheal development: molecular mechanisms .............................................................................................. 8
11.7.2.6 Tracheal and vascular development: parallels ................................................................................................ 9
11.7.3 LUNG ...................................................................................................................................................................... 10
11.7.3.1 lung development ......................................................................................................................................... 10
11.7.3.2 Lung development: molecular mechanisms .................................................................................................. 11
11.7.3.3 Lung development: different solutions ......................................................................................................... 11
11.7.4 KIDNEY ................................................................................................................................................................... 12
11.7.4.1 Kidney development...................................................................................................................................... 12
11.7.4.2 Kidney development: molecular mechanisms ............................................................................................... 12
11.7.5 MAMMARY GLAND .................................................................................................................................................... 14
11.7.5.1 Stages of mammary gland development ...................................................................................................... 14
11.7.5.2 Mammary gland: molecular mechanisms ..................................................................................................... 15
11.8 BRANCHING MORPHOGENESIS: COMMON THEMES ............................................................................................15
11.9 THREE EXAMPLES OF GENETIC DISRUPTIONS .......................................................................................................16
11.9.1 DISEASE OF THE LUNG................................................................................................................................................. 16
11.9.2 DISEASE OF THE KIDNEY .............................................................................................................................................. 16
11.9.3 DISEASE OF THE MAMMARY GLAND ............................................................................................................................... 16
1
,Goals:
• To know where branched structures occur and what the role is of the branching
• To define branching morphogenesis
• To distinguish branching modes
• To know the experimental approaches to study branching morphogenesis
• To know the key events and molecular mechanisms regulating 5 different types of branching morphogenesis
• To be able to identify common mechanisms
• To be able to link congenital disorders to developmental mechanisms of branching morphogenesis
11. 1 BRANCHED STRUCTURES: WHERE AND WHY?
• Branched tissue architecture is universally conserved
• It’s in plants (leaves of a tree), animals, single cells (bv neurons)
• Branching can occur in a single cell or with a group of cells. If we think about neurons we have automatically
intercellular connectivity and so that allows rapid and target the long-distance exchange of information. Groups
of cells that organize themselves in larger scale branch structures.
• In tissues/organs that require a high surface to volume ratio for their function. It changes the ratio (surface to
volume) relatively small volume correspondent to a large surface. Necessary? In essence to exchange material
(bv lungs: gas exchange) The presence of a large surface relative to volume makes the rapid and easy exchange
of materials in the broad sense. It’s important for the function of the organs.
High surface to volume ratio for their function :
o import to or from organism
o transport to or from organism
o secretion to or from organism
Examples (in the slides):
• nervous system
• blood vessels
• tracheal system
• lung
• kidney
• mammary gland
11.2 BRANCHED STRUCTURES: FUNCTION AND STRUCTURE
• Branched tissue architecture is universally conserved
• In tissues/organs that require a high surface to volume ratio for their function
o import, transport or secretion of materials to or from organism
o Vasculature: delivery of oxygen and nutrients, removal of metabolic waste
o Tracheal system: gas exchange
o Lung: gas exchange
2
, o Kidney: removal of metabolic waste, urine
o Mammary gland: milk
• The central structure of branched organs is composed of tighty associated epithelial cells surrounded by
loosely connected mesenchymal cells.
→ It’s the information exchange so the instructive signals from the mesenchymal cells to the epithelial cells,
that helps shape the branching pattern of the organ.
11.3 BRANCHING MORPHOGENESIS: DEFINITION
Branching morphogenesis
= the developmental process whereby a cell or a group of cells expands its surface area by forming cellular or tissue
extensions during development.
When talking about single cells we think about neurons, when talking about groups of cellswe think about
the examples we will discuss further underneath.
11.4 BRANCHING MORPHOGENESIS: STUDIED USING COMBINATION OF APPROACHES
These are the examples we will look at:
• Genetics (mouse, zebrafish, Drosophila)
• Characterization of causal genes for inherited disorders
• Tissue recombination experiments (old approach). You have the epithelial component and the
mesenchymal component. It is the instructive signals coming from the mesenchymal component that leads
to the branching pattern for the organ.
• Cell fate mapping
• Mosaic analysis
• Live imaging of organ cultures
11.5 BRANCHING MORPHOGENESIS: MODES OF BRANCHING
There are 3 modes of branching: 1 and 2 are the principal modes of branching.
1) Bifurcation = the tip of a structure splits in 2. Splitting of an existing tip in two or more daughter branches
2) Lateral branching = formation of a new bud (on the side of existing bud) that is extended from a preexisting
branch.
What can come on top of that is that while the structure is following that, that there is also a:
3) Rotation: this rotation makes that you can actually can generate 3D structures.
This is a question that can come on the exam: what are the modes of branching?
3
P. CALLAERTS
INHOUDSOPGAVE
11. 1 BRANCHED STRUCTURES: WHERE AND WHY? ...................................................................................................... 2
11.2 BRANCHED STRUCTURES: FUNCTION AND STRUCTURE ........................................................................................ 2
11.3 BRANCHING MORPHOGENESIS: DEFINITION ......................................................................................................... 3
11.4 BRANCHING MORPHOGENESIS: STUDIED USING COMBINATION OF APPROACHES .............................................. 3
11.5 BRANCHING MORPHOGENESIS: MODES OF BRANCHING ...................................................................................... 3
11.6 BRANCHING MORPHOGENESIS: EVENTS AND REGULATION ................................................................................. 4
11.7 5 CASES ................................................................................................................................................................. 4
11.7.1 VASCULATURE ............................................................................................................................................................ 4
11.7.1.1 Vasculogenesis and angiogenesis ................................................................................................................... 4
11.7.1.2 Stages of vasculature development ................................................................................................................ 5
11.7.1.3 Vasculature development: cellular and molecular basis ................................................................................. 5
11.7.2 TRACHEAL SYSTEM....................................................................................................................................................... 7
11.7.2.1 Different stages of tracheal development: embryogenesis ............................................................................ 7
11.7.2.2 Different stages of tracheal development: metamorphosis ........................................................................... 7
11.7.2.3 Tracheal development: cellular basis .............................................................................................................. 7
11.7.2.4 Tracheal development: genetics ..................................................................................................................... 8
11.7.2.5 Tracheal development: molecular mechanisms .............................................................................................. 8
11.7.2.6 Tracheal and vascular development: parallels ................................................................................................ 9
11.7.3 LUNG ...................................................................................................................................................................... 10
11.7.3.1 lung development ......................................................................................................................................... 10
11.7.3.2 Lung development: molecular mechanisms .................................................................................................. 11
11.7.3.3 Lung development: different solutions ......................................................................................................... 11
11.7.4 KIDNEY ................................................................................................................................................................... 12
11.7.4.1 Kidney development...................................................................................................................................... 12
11.7.4.2 Kidney development: molecular mechanisms ............................................................................................... 12
11.7.5 MAMMARY GLAND .................................................................................................................................................... 14
11.7.5.1 Stages of mammary gland development ...................................................................................................... 14
11.7.5.2 Mammary gland: molecular mechanisms ..................................................................................................... 15
11.8 BRANCHING MORPHOGENESIS: COMMON THEMES ............................................................................................15
11.9 THREE EXAMPLES OF GENETIC DISRUPTIONS .......................................................................................................16
11.9.1 DISEASE OF THE LUNG................................................................................................................................................. 16
11.9.2 DISEASE OF THE KIDNEY .............................................................................................................................................. 16
11.9.3 DISEASE OF THE MAMMARY GLAND ............................................................................................................................... 16
1
,Goals:
• To know where branched structures occur and what the role is of the branching
• To define branching morphogenesis
• To distinguish branching modes
• To know the experimental approaches to study branching morphogenesis
• To know the key events and molecular mechanisms regulating 5 different types of branching morphogenesis
• To be able to identify common mechanisms
• To be able to link congenital disorders to developmental mechanisms of branching morphogenesis
11. 1 BRANCHED STRUCTURES: WHERE AND WHY?
• Branched tissue architecture is universally conserved
• It’s in plants (leaves of a tree), animals, single cells (bv neurons)
• Branching can occur in a single cell or with a group of cells. If we think about neurons we have automatically
intercellular connectivity and so that allows rapid and target the long-distance exchange of information. Groups
of cells that organize themselves in larger scale branch structures.
• In tissues/organs that require a high surface to volume ratio for their function. It changes the ratio (surface to
volume) relatively small volume correspondent to a large surface. Necessary? In essence to exchange material
(bv lungs: gas exchange) The presence of a large surface relative to volume makes the rapid and easy exchange
of materials in the broad sense. It’s important for the function of the organs.
High surface to volume ratio for their function :
o import to or from organism
o transport to or from organism
o secretion to or from organism
Examples (in the slides):
• nervous system
• blood vessels
• tracheal system
• lung
• kidney
• mammary gland
11.2 BRANCHED STRUCTURES: FUNCTION AND STRUCTURE
• Branched tissue architecture is universally conserved
• In tissues/organs that require a high surface to volume ratio for their function
o import, transport or secretion of materials to or from organism
o Vasculature: delivery of oxygen and nutrients, removal of metabolic waste
o Tracheal system: gas exchange
o Lung: gas exchange
2
, o Kidney: removal of metabolic waste, urine
o Mammary gland: milk
• The central structure of branched organs is composed of tighty associated epithelial cells surrounded by
loosely connected mesenchymal cells.
→ It’s the information exchange so the instructive signals from the mesenchymal cells to the epithelial cells,
that helps shape the branching pattern of the organ.
11.3 BRANCHING MORPHOGENESIS: DEFINITION
Branching morphogenesis
= the developmental process whereby a cell or a group of cells expands its surface area by forming cellular or tissue
extensions during development.
When talking about single cells we think about neurons, when talking about groups of cellswe think about
the examples we will discuss further underneath.
11.4 BRANCHING MORPHOGENESIS: STUDIED USING COMBINATION OF APPROACHES
These are the examples we will look at:
• Genetics (mouse, zebrafish, Drosophila)
• Characterization of causal genes for inherited disorders
• Tissue recombination experiments (old approach). You have the epithelial component and the
mesenchymal component. It is the instructive signals coming from the mesenchymal component that leads
to the branching pattern for the organ.
• Cell fate mapping
• Mosaic analysis
• Live imaging of organ cultures
11.5 BRANCHING MORPHOGENESIS: MODES OF BRANCHING
There are 3 modes of branching: 1 and 2 are the principal modes of branching.
1) Bifurcation = the tip of a structure splits in 2. Splitting of an existing tip in two or more daughter branches
2) Lateral branching = formation of a new bud (on the side of existing bud) that is extended from a preexisting
branch.
What can come on top of that is that while the structure is following that, that there is also a:
3) Rotation: this rotation makes that you can actually can generate 3D structures.
This is a question that can come on the exam: what are the modes of branching?
3
