L22: Morphogenesis Flashcards

1
Q

morphogenesis

A

generation of shape, size, and structure (e.g. organized form) during development

gastrulation, neurualtion, organogenesis

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2
Q

epithelial cells

A

joined together side by side (forming sheets and tubes)

epidermis, inside stomach/intestines

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3
Q

mesenchymal cells

A

loosely aggregated; can migrate as individuals form connective “tissue”

extracellular matrix proteins

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4
Q

morphogenesis occurs through these cell behaviors…

A
  • the direction and number of cell divisions
  • cell shape changes
  • cell growth
  • cell adhesion
  • cell movement
  • cell death
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5
Q

example of an organ: skin

A

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

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6
Q

epithelial cells form several types of junctions: tight junction, adherens junction, desmosome, gap junction, hemidesmosome

A
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7
Q

Cytoskeletal linkages between junctions distribute stress across cells

A

Mechanical stresses are transmitted from cell to cell by cytoskeletal filaments anchored to cell-cell and cell-matrix adhesion site

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8
Q

cadherins are a major component of adherens junctions

A

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)

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9
Q

assembly of an adherens junction

A
  1. membrane protrusions intitiate cell-cell contact
  2. actin and cadherin recruitment expands junction
  3. actin remodeling and myosin recruitment expands the adherens junction

cadherin is essential for frog blastula formation

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10
Q

Cadherins mediate homotypic interactions

A

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

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11
Q

holfreter’s experiment showing that cells can “sort out”

A
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12
Q

cadherin-dependent cell sorting

A

the more interacting cadherins on the apposing cell surfaces, the tighter the adhesion. Cells with stronger
adhesion pack more tightly and stay inside.

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13
Q

epithelial sheets can bend to form a tube (neural tube)

A
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14
Q

cadherins expression changes in neurulation promote morphogenetic movements

A
  1. 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
  2. Cadherin 6b comes on in the neural fold
    Delineating the future pre-migratory neural crest domain
    Invagination continues and =>pinching off the neural tu
  3. 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

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15
Q

failure of neural tube closure in human causes birth defects

A

Spina bifida
Anencephaly

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16
Q

epithelial-mesenchymal transition (EMT)

A

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

17
Q

what is the basal lamina

A

-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

18
Q

what are integrins

A

-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.

19
Q

fibronectin-integrin interaction is critical for gastrulation

A

Fibronectin coats the basal surface of the blastocoel roof

Migrating mesoderm cells express integrin and migrate along the roof

20
Q

fibronectin-integrin interaction is critical for mesoderm migration

A

Disrupting fibronectin-integrin interaction disrupts mesoderm migration