Tissue dynamic and MorphogenesisTissue dynamic and Morphogenesis

Dept. PhysiologyChang Gung University

J. K. Chen, Professor

MorphogenesisMorphogenesis

Morphogenesis refers to the structural chaMorphogenesis refers to the structural changes and its underlying mechanismsnges and its underlying mechanisms

Morphogenic processes are important in tiMorphogenic processes are important in tissue dynamics, and in practical aspects of ssue dynamics, and in practical aspects of tissue reconstruction, repair and engineeritissue reconstruction, repair and engineeringng

Dynamic state of tissuesDynamic state of tissues

Tissue homeostasis: the normal steady-state Tissue homeostasis: the normal steady-state function of tissue.function of tissue.Tissue repair: the integration procedure folloTissue repair: the integration procedure following grafting of tissue is expected to display wing grafting of tissue is expected to display components of tissue repair processes.components of tissue repair processes.Tissue formation: the way tissues form is of kTissue formation: the way tissues form is of key concern to cellular therapies. The younger ey concern to cellular therapies. The younger the cell source, the more organogenic potentithe cell source, the more organogenic potential it possesses.al it possesses.

Processes that lead to the evolution Processes that lead to the evolution of a functional tissueof a functional tissue

Induction : many tissues will not begin to Induction : many tissues will not begin to develop until cells of different types come into develop until cells of different types come into physical contact with one another.physical contact with one another.

Once they are in contact, at least one of the Once they are in contact, at least one of the layers of the two tissue types undergoes layers of the two tissue types undergoes reorganization.reorganization.

The presence of one cell type is needed to The presence of one cell type is needed to induce a change in the other.induce a change in the other.

TransdifferentiationTransdifferentiation

Adult cell can transdifferentiate from one cAdult cell can transdifferentiate from one cell type to another. In particular, mesenchyell type to another. In particular, mesenchyme and epithelial can transform due to expme and epithelial can transform due to expression of a variety of genes.ression of a variety of genes.

These transdifferentiation pathways are of These transdifferentiation pathways are of importance to tissue engineering.importance to tissue engineering.

Cellular processes involved in Cellular processes involved in morphogenesismorphogenesis

Cell migrationCell migration

Tissue sortingTissue sorting

Tissue patterning by cell deathTissue patterning by cell death

Cell migrationCell migration

Bone marrow stem cells can be induced to Bone marrow stem cells can be induced to migrate out of the marrow into blood circulmigrate out of the marrow into blood circulation by infusing chemotactic growth factoration by infusing chemotactic growth factors into the patient.s into the patient.

Changes in cell-cell adhesion may initiate tChanges in cell-cell adhesion may initiate the migration of a cell population.he migration of a cell population.

Mobilization and homing

J Clin Invest., 115, 572, 2005

Biochemical process of cell Biochemical process of cell migrationmigration

Step 1 : protrusion of membrane lamellopodia, loStep 1 : protrusion of membrane lamellopodia, local actin polymerization plays an important role.cal actin polymerization plays an important role.Step 2 : adhesion to the matrix occurs via integriStep 2 : adhesion to the matrix occurs via integrins, providing a link to the actin cytoskeleton.ns, providing a link to the actin cytoskeleton.Step 3 :contraction of the cytoplasm by myosin bStep 3 :contraction of the cytoplasm by myosin based-motor.ased-motor.Step 4 : rear release and cell displacementStep 4 : rear release and cell displacementStep 5 : the remaining integrins are recycled by Step 5 : the remaining integrins are recycled by endocytosis and intracellular diffusion of the inteendocytosis and intracellular diffusion of the integrin vesicles to the leading edge.grin vesicles to the leading edge.

Cellular processes involved in morphogenesis

Initiation of morphogenesisInitiation of morphogenesis

To initiate the morphogenic process, the prTo initiate the morphogenic process, the present state (the initial cellular arrangemenesent state (the initial cellular arrangement) must be destabilized.t) must be destabilized.

Some of the initial molecular processes duSome of the initial molecular processes during morphogenesis are those involved in tring morphogenesis are those involved in the expression of surface protein and alterahe expression of surface protein and alteration in the extracellular matrix.tion in the extracellular matrix.

Cell deathCell death

Programmed cell death : cells have to die if they don’t Programmed cell death : cells have to die if they don’t pass certain check point in the cell cycle. For instance,pass certain check point in the cell cycle. For instance, cells need to die in a controlled fashion to produce the cells need to die in a controlled fashion to produce the finger pattern during development.finger pattern during development.Biochemically, there are 2 major events involved : Biochemically, there are 2 major events involved :

a cascade of caspase activation.a cascade of caspase activation. a loss of mitochondrial membrane function.a loss of mitochondrial membrane function. a large opening in the mitochondrial a large opening in the mitochondrial membrane marks the point of no return inmembrane marks the point of no return in this process.this process.

Unerlying biochemical processUnerlying biochemical process

Three different mode of apoptosis inductioThree different mode of apoptosis induction : 1. an external murder signaln : 1. an external murder signal

2. removal of an extracellular 2. removal of an extracellular

survival signalsurvival signal

3. a “suicide” program initiated 3. a “suicide” program initiated

by an external stressby an external stress

Fas signaling and mechanism of blocking by DcFas signaling and mechanism of blocking by DcR3 : malfuntion of cell signaling leads to breakdR3 : malfuntion of cell signaling leads to breakd

own of normal cell- coordination processown of normal cell- coordination process