Bio 325 Final

Front 1

Surface Ectoderm structures

Back 1

Epidermis, Lens, cornea, teeth

Front 2

Neural crest structures

Back 2

PNS, melanocytes, facial cartilage, head bones

Front 3

Neural Tube

Back 3

CNS, motor neurons, retina.

Front 4

Primary neurulation
Shaping

Back 4

-Neural plate forms (BMP inhibition)
-Convergent-extension movements (actin cytoskeleton)

Front 5

Primary neurulation
Folding Elevation

Back 5

-MHP formation (actin cytoskeleton, BMP inhibition response)
-ventral midline elongates

Front 6

Primary neurulation
Convergence

Back 6

-Neural folds are pushed together by epidermis
-DLHP form (actin cytoskeleton)

Front 7

Primary neurulation
Closure

Back 7

-Separation from dorsal ectoderm
-caused by change in cadherin (NT expresses N, ectoderm = E)

Front 8

Actin Cytoskeleton

Back 8

Causes constriction change in cell shape

Front 9

Microtubules

Back 9

Causes elongation in cell shape

Front 10

Knockdown of N-cadherin

Back 10

-Neural plate will not fold correctly
-Will also not separate from ectoderm

Front 11

Neural tube closure in humans

Back 11

-Multiple closure points
-TFs: Pax3, Shh and openbrain

Front 12

Folic acid (folate)

Back 12

-Folate binding protein in neural folds during closure
-Adding to diet reduces occurrence of neural tube defects

Front 13

Folic acid and Thymidine

Back 13

-In Pax3 -/-:
-Thymidine + Folic acid reduce neural tube defects
-Promote DNA replication and cell division
-Methionine causes more defects.

Front 14

Anterior Neuroectoderm

Back 14

Specified by inhibition of Wnt, BMP, and Nodal
-Goosecoid+Hex (anterior mesoderm) -> DKK + Cer (ant. mesoderm)->Hesx1, Lim1, Bf1, Otx2 (Ant. Neuroect.) -l BMP, Wnt, Nodal

Front 15

AVE

Back 15

-In mouse
-Migrates anteriorly
-Induces anterior expression, suppresses posterior
-Cer + DKK -> Hesx1, Otx2, Lim1
-Cer + DKK -l WNT, FGF, Retinoic acid (posterior trans factors)

Front 16

Otx2, Lim1, Hesx1

Back 16

Loss of 1 leads to loss of head structures.

Front 17

Chordin + Noggin

Back 17

-BMP inhibitors
-Functionally redundant = loss of 1 will not lead to significant defects. Need loss of both to see effects (loss of anterior plane + cyclopia)

Front 18

Posterior Neuroectoderm

Back 18

-Specified by gradients of Wnt, Fgf, and RA
-Dose dependent activation of Cdx2 -> Hox

Front 19

Wnt (overexpression)

Back 19

-Upregulation = more posterior formation
-smaller brain (loss of anterior brain structures)
-more spinal cord
-less Otx2, Bf1
-More Krox20

Front 20

Wnt (underexpression)

Back 20

-Larger forebrain
-More Otx2, Bf1
-Less Krox20
-Less spinal cord

Front 21

Wnt3a -/-

Back 21

-diminished posterior development
-Brain develops
-Spinal cord truncated

Front 22

RA exposure

Back 22

-Inhibits AVE localization
-No cell migration
forms 2 primitive streaks.

Front 23

Expansion of Brain region

Back 23

-NT closes temporarily
-Fills with cerebrospinal fluid
-closing of posterior directional anterior expansion

Front 24

Forebrain

Back 24

-Otx2 expression
-> telencephalon + diencephelon (Eye formation)

Front 25

Midbrain

Back 25

-Engrailed (En) expression
-Mesencephalon (does not change)

Front 26

hindbrain

Back 26

-Spinal cord
-Krox20 + hox expression

Front 27

Neural tube epithelium

Back 27

-Can split symmetrically or assymetrically.
-Sym - both cells maintain basal contact. Produces 2 neural stem cells
-Assym - Only 1 cell maintains basal contact (stem). Produces 1 stem cell and 1 neuron or glia.
-Assym = Differentiation!

Front 28

NT zones

Back 28

Ventricular
-stem cells
Intermediate
-Gray matter
-Differentiating cells (neurons and glia)
Marginal
-Few cells
-mostly axons
-white matter

Front 29

Fgf10 -/-

Back 29

-Brain expansion
-Maintains polarity
-more symmetrical division = more stem cells.
-Less differentiation

Front 30

Optic cup

Back 30

-Induces SE -> lens vesicle -> cornea
-will occur ectopically
-Upreg of transcr. factors will induce ectopic eye tissue

Front 31

Rx1 -/-

Back 31

-No eye develpment
-Specified optic cup
-very upstream

Front 32

Pax6 +/- and -/-

Back 32

+/- = no iris. usually causes multiple other negative effects.
-/- = lethal. No eye formation. Missing other face structures.
-Pax6 is well conserved across species (flies, mice, humans)

Front 33

Optic vesicle and lens formation

Back 33

-Diencephalon outpockets
-Rx1, Pax6, Otx2, Sox1 (indicates brain formation) expressed.
-OV secretes BMP4-> induces lens formation from SE (along with Notch).
-BMP = Smad dependent pathway.
-BMP -> Sox2
-Sox2 + Pax6-> crystallinv gene (lens differentiation)
-Notch + Otx2 -> Lens1 TF (cell differentiation + lens closure)

Front 34

OV formation 2

Back 34

-OV folds on itself
-2 layered retina is formed (top layer is neural, bottom is pigment)
-Wnt3a signalling causes retina to fold and form.
-Retina is stratified
-Notch inhibition will cause more differentiation of stem cells.

Front 35

Cornea differentiation

Back 35

-Lens vesicle induces SE to become cornea
-Neural crest cells migrate to space bet lens and SE and release collagen
-organize in the corneal endothelium

Front 36

lens differentiation

Back 36

-dividing cells from the anterior migrate posteriorly and stop dividing.
-Detaches from the cornea
-lens vesicle region fills with cells.
-division stops and nucleus is extruded (removed)

Front 37

Iris differentiation

Back 37

-2 parts
Anterior - Neural crest cells. Level of Pigmentation determines eye color/shade.
Posterior - Non-neural retina cells. Always pigmented.
-Cilliary body - Holds lens in place, adjusts lens focus. Muscles are from non-neural ectoderm (not mesoderm)

Front 38

Shh (eye)

Back 38

-Splits eye field in 2
-divides the brain into left and right hemispheres.
-Expressed in the prechordal plate.
-Shh -> Ptc2-l Pax2
-overexpression of Shh and Ptc2 causes lack of eyes in cave fish. Pax2 is downregulated.

Front 39

Shh (eye) 2

Back 39

-Loss of Shh -> loss of separation -> cyclopia and holoprosencephaly (no brain hemisphere division).
-loss of noggin and chordin will also cause cyclopia.

Front 40

Shh, BMP in the NT

Back 40

-Dorsal-ventral axis is gradient determined
-BMP is dorsal determinant (from ectoderm) - Roof plate
-Expression of TF: BMP4 (most dorsal, 5, 7 (More ventral than 4), Dorsalin, Activin (TGFB ligands).
-Shh is ventral determinant (from notochord) - Floor plate
-specifies motor neurons.

Front 41

Shh, BMP in the NT 2

Back 41

Pax7 - inhibited by low Shh (very dorsal)
Pax6 - Inhibited by high Shh (more ventral)
Nkx 6.1 - Activated by moderate Shh
Nkx2.2 - Activated by high Shh

Front 42

Shh, BMP in the NT 3

Back 42

Pax7 - Dorsal interneur.
Lim1/2 - expressed as a result of Pax7
Dorsalin - Roofplate + interneurons.
Pax6 - interneurons + motor neurons
Isl 1/2 - Motor neurons
Nkx6.1 - V3 neurons
Shh - floorplate + notochord

Front 43

Shh inhibition -> cyclopia

Back 43

-Jervine, cyclopamine, cholesterol metabolites, and cholesterol interfering drugs and primary cilia mutations will induce cyclopia
-Loss of midline tissue.
-Causes inhibition of Shh.
-NT ventralizes.
-Alters somite development
-interferes with Smoothened receptor -> no reaction to Shh
-Promotes apoptosis and represses proliferation
-smoothened cannot activate gli2A to transcribe Shh gene targets.
-Loss of cilia has similar effect.

Front 44

Fetal alcohol syndrome

Back 44

-Alcohol metabolism produces superoxide radicals, which causes cell death in embryo
-Alcohol inhibits cell adhesion.
-Less adhesion in higher concentrations.