Pathways

Question 1

How are the reproductive systems formed?

Answer 1

Female is the default pathway, but both the Mullerian Duct and the Wollfian Duct begin to form. In the male, Mullerian Inhibiting Substance causes the Mullerian Duct to regress, and Testosterone causes the Wolffian Duct to mature. In female (without these 2 hormones), Wollfian Duct regresses, and the number of oocytes decrease via apoptosis before birth.

Question 2

What is the extrinsic pathway for apoptosis?

Answer 2

FAS ligand (T-cell) binds FAS receptor (cell)
Caspase 8 is activated

This pathway occurs after birth and after the immune system develops

Question 3

What is the intrinsic pathway of apoptosis?

Answer 3

Anti-apoptotic BCL2 blocks cytochrome C release by binding BAK
Pro-apoptotic BAX and BIM enter mitochondria and release BAK from BCL2
BAX and BAK poke holes in mitochondria, releasing cytochrome C
Cytochrome C activates APAF1, which activates Caspase-9 (initiator), which activates Caspase-3 (effector), which causes cell death.

Question 4

Define: Caspase

Answer 4

Cysteine protease that cleaves after Aspartate residues. Caspases cause cell death.

Question 5

How are the digits formed?

Answer 5

BMP7 activates MSX, which inhibits FGF; cell death occurs

Question 6

How is it decided whether ectoderm should become CNS or skin?

Answer 6

Wnt activates BMP, allowing skin to form

FGF inhibits BMP, causing CNS formation

(week 4)

Question 7

How is it decided whether skin is hairy or non-hairy?

Answer 7

Wnt = hairy
BMP activates Notch = non-hairy (“bare and nude”)

Weeks 7-21

Question 8

How does hair follicle develop?

Answer 8

EDA to Wnt10b causes placode formation
Placode makes Shh, which drives cell proliferation, causing bud
Dkk1 inhibits Wnt, which means that hair growth is only localized

Question 9

How does the enteric nervous system form?

Answer 9

NC cells migrate to and colonize the gut.
NC cell w/ RET follow GDNF gradient to origin in cecum.
To migrate past the cecum, NC cells must express endothelin3 and bind Ednrb (inhibits differentiation, thus promoting migration)

Question 10

What causes NC migration?

Answer 10

RhoB expression, which causes actin polymerization and microfilament insertion, resulting in movement

Question 11

How do signaling factors affect rostral/caudal identity?

Answer 11

Rostral = low RA concentration, low Hox # expressed
Caudal = high RA concentration, high Hox # expressed

Question 12

How do signaling factors affect anterior/posterior identity?

Answer 12

FGF is most anterior and posterior
Shh is at that Thalamus
Wnt is at the Midbrain

Question 13

How do signals affect dorsal/ventral identity?

Answer 13

Dorsal: high BMP, low Shh
Ventral: low BMP, high Shh

Question 14

Which signals are axon-attract? Repulsive? Long range? Short range?

Answer 14

Attractive: Netrin (long range), Laminin (short-range)
Repulsive: Slits/Robo (long-range), Ephrin (short-range) and Semaphorins/Plexins (short-range)

Question 15

What does Ihh do?

Answer 15

Required for chondrocyte proliferation and maturation

KO causes normal skeletal shape, but smaller bones

Question 16

What does PTHrP do?

Answer 16

Inhibits Ihh, slows maturation of chondrocytes into hypertrophic chondrocytes that die and are replaced by bone

KO causes normal skeletal shape, but smaller bones (less severe than Ihh KO)

Question 17

What does Atf4 do?

Answer 17

Regulates expression of osteoblasts during the later stages

decreased Atf4 causes Coffin-Lowry syndrome (treat with more protein)
increased activation causes fNeurofibromatosis Type I (treat with less protein)

Question 18

What initiates limb growth?

Answer 18

FGF

Question 19

What causes development of the forelimb? Hindlimb?

Answer 19

Forelimb: Tbx5
Hindlimb: Tbx4+Pitx1

Question 20

Define: Apical Ectodermal Ridge (AER)

Answer 20

Responsible for proximal/distal development
FGF4, 8, and 9 are expressed
Wnt/FGFs promote distal features
RA promotes proximal features

Question 21

Define: Zone of Polarizing Activity (ZPA)

Answer 21

Responsible for anterior/posterior, found on posterior edge and secretes Shh
Gli3 constrains to 1 digit, Shh inhibits Gli3 and allows 5 digits to form
Baseline is lots of fingers!

Question 22

How is ventral/dorsal regulated?

Answer 22

En-1 causes ventral

Wnt7a and Lmx-1 cause dorsal

Question 23

How does the oscillatory clock work?

Answer 23

Delta turns on Notch, turns on segmentation

Lunatic fringe Inhibits Notch to turn off

To resent, Hes1,7 inhibits itself and Lunatic Fringe

Question 24

What does RA do in segmentation and somitogenesis?

Answer 24

Is transiently secreted from rostral end from somites and sharpens the border

Question 25

Define: homeobox

Answer 25

DNA sequence that encodes homeodomain

Question 26

Define: homeodomain

Answer 26

Protein sequence that acts as transcription factor during development

Question 27

What do the Hox #s mean?

Answer 27

Hox 1-9: thoracic
1-10: lumbar
1-11: sacral

Question 28

What factor makes hES best for use?

Answer 28

Blimp1

Question 29

Define: SCNT cells

Answer 29

Transfer of nuclei from somatic cell to oocyte (ex - fix mitochondrial defect for child)

Question 30

Define: iPS cells

Answer 30

Reprogrammed somatic cells through use of transcription factors normally active in undifferentiated cells
Note: might retain epigenetic memory

Question 31

Match Hedgehog (Xhh) with its other players

Answer 31

Binds Ptch, activates Smo, activates Gli

Question 32

Match TGF with other players

Answer 32

TGF + BMP goes with Smad/Co-smad and LOTS of ligands

Question 33

Match Wnt with other players

Answer 33

Frizlled, beta catenin, Tcf/Lef (prevents beta catenin degradation)

Question 34

Match FGF with other players

Answer 34

Serine/threonine cascade, Ras

On/off signal (NOT dose-dependent)