Developmental Biology 6- Morphogenesis: Neural Tube Formation Cell Migrations

Front 1

The Nervous System

Back 1

Central NS: brain and spinal cord
Peripheral NS: neurons outside the CNS

Front 2

Peripheral NS

Back 2

sensory neurons (DRGs)
motor neurons
autonomic NS: sympathetic, parasympathetic, enteric

Front 3

Neural Tube Formation

Back 3

Neural tube
Neural crest cells
Anterior tube forms as shown
Posterior of "tube" develops as a solid rod of cells

Front 4

The Notochrod Influences Neural Tube Formaiton

Back 4

Signals from the notochord induce cell shape changes in the neural plate
The notochord also organizes the D/V patterning of the neural tube.

Front 5

Problems with Tube Closure

Back 5

Anencephaly
Spina Bifida

Front 6

Anencephaly

Back 6

Severe defect in neural tube closure
Brain cannot form properly: absent or malformed at birth

Front 7

Spina Bifida

Back 7

Partial defect in neural tube closure
Usually a lack of fusion in the region forming the spinal cord
Born with an opening to the spinal cord

Front 8

Neural Tube Formation

Back 8

Driven by changes in cell shape and cell migration
Elongation, narrowing and apical constriction
Movements of the neural plate cells and the ectoderm

Front 9

Apical Constrictions

Back 9

Occur at hinge points
Hinge points occur within the neural fold/neural furrow

Front 10

Neural Tube Formation

Back 10

Doesn't occur at the smae time along the A/P axis
Starts in the region of the midbrain
Actin cytoskeleon important for the neural tube formation in the head region (cytochalasin) but not the spinal cord region

Front 11

cytochalasin

Back 11

head region where the actin cytoskeleton is important for neural tube formation

Front 12

Shroom

Back 12

Mouse gene identified in a gene trap mutagenesis screen
Phenotype: Developing brain bulges out of the head like a mushroom
Shroom is a novel actin-binding protein
Expressed in the apical regions of the neural plate cells
causes constrictions and folding when expressed in epithelial cells
Important control protein?

Front 13

Tube Formation: changes in cell adhesion

Back 13

Ectoderm and neural plate express L-CAM
As the neural folds develop the nueral plate expresses N-cadherin and N-CAM
The ectoderm expresses E-cadherin
Allows the neural plate to separate from the surrounding ectoderm

Front 14

Neural Crest Cells

Back 14

Come from the edges of the floor plate and/or the dorsal neural tube
Give rise to: cartilage, pigment cells, medullary cells, schwann cells, neurons: PNS
BMP threshold required to initiate movement

Front 15

Following Neural Crest Cell Migrations

Back 15

Use chick-quail chimeras
Graft a piece of neural tube from one animal to another
Nicole Le Douarin

Front 16

Neural Crest cells form the Hindbrain

Back 16

Neural crest cells from rhombomeres r1 and r2 migrate to branchial arch b1; r4 to b2; r6 to b3
These cells in the branchial arches give rise to cells that form the bones and cartilage of the jaw and the inner ear

Front 17

Neural Crest Cells: Changes in Cell Adhesion

Back 17

Neural plate expresses N-cadherin
Cadherin-6 expressed in the neural crest generating regions
When the neural crest cells leave the neural tube the expression switches to cadherin-7; N-cadherin and cadherin-6 no longer expressed
probably involved in the segregation of cells

Front 18

Two Main Migratory Pathways

Back 18

Dorso-lateral pathway
Ventro-lateral pathway

Front 19

Dorso-lateral pathway

Back 19

migrating cells travel over the somites
cells mainly give rise to pigment cells (melanocytes)

Front 20

ventro-lateral pathway

Back 20

cells migrate into the somites
give rise to: sypathetic ganglia, DRGs, medullary cells

Front 21

Cells Cannot Migrate Through the Posterior of the Somite

Back 21

Ventro-lateral pathway cells only travel through the anterior
This sets up the segmental arrangement of the DRGs along the spinal cord
This restriction due to the properties of the somite
Experiment?
EphrinB1 is expressed in the posterior of somites

Front 22

Other Factors Affecting Neural Crest Cell Migrations

Back 22

The neural tube: influences the direction of migration, flip dorso-ventrally, cells now migrate dorsally, something secreted from neural tube?
The notochord: repels migrating neural crest cells over a short range, something secreted from the notochord?
Extracellular matrix: blocking integrin funciton can inhibit cell migrations, cells adhere to and migrate on ECM components

Front 23

Dictyostelium Aggregation

Back 23

Involves chemotaxis and signal propagation
Cells adhere to one another at their anterior and posterior cells

Front 24

cAMP is the Chemoattractant

Back 24

Cells move up a concentration gradient of cAMP
Extend a pseudopod in the direction of the cAMP to initiate migration
Actin and myosin regulated for movement

Front 25

Signal Propagation

Back 25

Gradients usually work over short distances (1mm)
cells can aggregate over distances of 5 mm because of signal propagation
The cAMP signal is propagated b/w cells down the stream
Cell recieves a signal then produces the signal itself

Front 26

Directed Dilation

Back 26

Hydrostatic force provides the force for morphogenesis
Applies to structures as well as individual cells
Example: notochord formation

Front 27

Development of the Notochord

Back 27

Presumptive notochord mesoderm is the one of the first tissues to internalize in gastrulation
Elongates by convergent extension and directed dilation
It is the first mesodermal sturcture to differentiate
Extracellular sheath around the notochord restricts the circumferential expansion
cells in the notochord expand (water uptake into vacuoles)
Expansion of the notochord occurs at the ends

Front 28

The C. elegans Embryo Elongates by Directed Dilation

Back 28

Decrease in circumference with an increase in length
Elongation occurs due to circumferential contraction of hypodermal cells
Experiments?

Front 29

Cell Enlargement is a Major Process in Plant Morphogenesis

Back 29

Large increases in tissue volume occur due to increases in cell size
Direction of growth determined by orientation of cellulose fibrils in the cell wall
how the fibrils are laid down by the cell controls the direction of elongation

Front 30

Mutations Affecting Leaf Formation

Back 30

WIld type, angustifolia mutation
rotundifolia mutation