L22: Morphogenesis Flashcards
generation of shape, size, and structure (e.g. organized form) during development
gastrulation, neurualtion, organogenesis
epithelial cells
joined together side by side (forming sheets and tubes)
epidermis, inside stomach/intestines
mesenchymal cells
loosely aggregated; can migrate as individuals form connective “tissue”
extracellular matrix proteins
morphogenesis occurs through these cell behaviors…
- the direction and number of cell divisions
- cell shape changes
- cell growth
- cell adhesion
- cell movement
- cell death
example of an organ: skin
epithelial cells:
-tightly packed together
-cell-cell junctions
-polarized (basal/apical)
mesenchymal cells:
-sparse, embedded in ECM
-generally no cell-cell junctions
-can migrate individually
Extracellular matrix:
-collagen
-fibronectin
-laminin
-basal lamina -> keeps epidermis anchored to dermis
epithelial cells form several types of junctions: tight junction, adherens junction, desmosome, gap junction, hemidesmosome
Cytoskeletal linkages between junctions distribute stress across cells
Mechanical stresses are transmitted from cell to cell by cytoskeletal filaments anchored to cell-cell and cell-matrix adhesion site
cadherins are a major component of adherens junctions
cadherins = Ca2+ sensitive adherence proteins
The extracellular (EC) domain of cadherin can bind to the EC domain of another cadherin
Binding requires Ca2+
The intracellular domain of cadherin is connected to the actin cytoskeleton via the catenin complex (alpha, beta, gamma)
assembly of an adherens junction
- membrane protrusions intitiate cell-cell contact
- actin and cadherin recruitment expands junction
- actin remodeling and myosin recruitment expands the adherens junction
cadherin is essential for frog blastula formation
Cadherins mediate homotypic interactions
homotypic interactions -> The same type of cadherins bind to each other, but not to other types of
cadherins (E binds to E, but not to N)
Different cell types express different types of cadherin: E-cadherin, P-cadherin, N-cadherin
holfreter’s experiment showing that cells can “sort out”
cadherin-dependent cell sorting
the more interacting cadherins on the apposing cell surfaces, the tighter the adhesion. Cells with stronger
adhesion pack more tightly and stay inside.
epithelial sheets can bend to form a tube (neural tube)
cadherins expression changes in neurulation promote morphogenetic movements
- Some E-cadherin+ cells begin to fold as they turn off
E-cadherin and on N-cadherin; The apical actin bundle
contracts and invagination begin - Cadherin 6b comes on in the neural fold
Delineating the future pre-migratory neural crest domain
Invagination continues and =>pinching off the neural tu - Neural crest cells downregulate Cadherin-6B and N-cadherin
Undergo EMT and migrate away from the neural tub
Mis-regulation of neural tube closure results in protrusions of the CNS through the epidermis
failure of neural tube closure in human causes birth defects
Spina bifida
Anencephaly
epithelial-mesenchymal transition (EMT)
Transformation of polarized epithelial cells to mesenchymal cells that can migrate and invade tissues
Mostly via down-regulation of cadherins
Important in development, wound healing and cancer metastasis
what is the basal lamina
-extracellular matrix (ECM) sheet
-secreted macromolecules that include proteoglycans, collagen, laminin, fibronectin
-Important for maintaining epithelial structure, cell migration, and cell signaling
-Can interact with cells via integrins, receptors for ECM proteins
-Create a bridge between epithelium and collagen-rich ECM below
ECM = Mostly insoluble proteins, forming sheet, fiber or gel-like structures
what are integrins
-link the ECM to the cytoskeleton
-Integrins are composed of a and b subunits
-Integrin activation exposes internal and external ligand-binding sites
-The external domain of integrin binds to the RGD motif (Arg-Gly-Asp) of ECM proteins (mostly fibronectin)
-The internal domain of integrin binds to talin/vinculin leading to organization of the actin cytoskeleton inside the cell
-For many cells, the ability to crawl through a tissue relies on grabbing fibronectin with its leading edge while releasing its grip at the lagging edge.
fibronectin-integrin interaction is critical for gastrulation
Fibronectin coats the basal surface of the blastocoel roof
Migrating mesoderm cells express integrin and migrate along the roof
fibronectin-integrin interaction is critical for mesoderm migration
Disrupting fibronectin-integrin interaction disrupts mesoderm migration
