Pathways Flashcards
How are the reproductive systems formed?
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.
What is the extrinsic pathway for apoptosis?
FAS ligand (T-cell) binds FAS receptor (cell) Caspase 8 is activated
This pathway occurs after birth and after the immune system develops
What is the intrinsic pathway of apoptosis?
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.
Define: Caspase
Cysteine protease that cleaves after Aspartate residues. Caspases cause cell death.
How are the digits formed?
BMP7 activates MSX, which inhibits FGF; cell death occurs
How is it decided whether ectoderm should become CNS or skin?
Wnt activates BMP, allowing skin to form
FGF inhibits BMP, causing CNS formation
(week 4)
How is it decided whether skin is hairy or non-hairy?
Wnt = hairy
BMP activates Notch = non-hairy (“bare and nude”)
Weeks 7-21
How does hair follicle develop?
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
How does the enteric nervous system form?
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)
What causes NC migration?
RhoB expression, which causes actin polymerization and microfilament insertion, resulting in movement
How do signaling factors affect rostral/caudal identity?
Rostral = low RA concentration, low Hox # expressed Caudal = high RA concentration, high Hox # expressed
How do signaling factors affect anterior/posterior identity?
FGF is most anterior and posterior
Shh is at that Thalamus
Wnt is at the Midbrain
How do signals affect dorsal/ventral identity?
Dorsal: high BMP, low Shh
Ventral: low BMP, high Shh
Which signals are axon-attract? Repulsive? Long range? Short range?
Attractive: Netrin (long range), Laminin (short-range)
Repulsive: Slits/Robo (long-range), Ephrin (short-range) and Semaphorins/Plexins (short-range)
What does Ihh do?
Required for chondrocyte proliferation and maturation
KO causes normal skeletal shape, but smaller bones
What does PTHrP do?
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)
What does Atf4 do?
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)
What initiates limb growth?
FGF
What causes development of the forelimb? Hindlimb?
Forelimb: Tbx5
Hindlimb: Tbx4+Pitx1
Define: Apical Ectodermal Ridge (AER)
Responsible for proximal/distal development
FGF4, 8, and 9 are expressed
Wnt/FGFs promote distal features
RA promotes proximal features
Define: Zone of Polarizing Activity (ZPA)
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!
How is ventral/dorsal regulated?
En-1 causes ventral
Wnt7a and Lmx-1 cause dorsal
How does the oscillatory clock work?
Delta turns on Notch, turns on segmentation
Lunatic fringe Inhibits Notch to turn off
To resent, Hes1,7 inhibits itself and Lunatic Fringe
What does RA do in segmentation and somitogenesis?
Is transiently secreted from rostral end from somites and sharpens the border
Define: homeobox
DNA sequence that encodes homeodomain
Define: homeodomain
Protein sequence that acts as transcription factor during development
What do the Hox #s mean?
Hox 1-9: thoracic
1-10: lumbar
1-11: sacral
What factor makes hES best for use?
Blimp1
Define: SCNT cells
Transfer of nuclei from somatic cell to oocyte (ex - fix mitochondrial defect for child)
Define: iPS cells
Reprogrammed somatic cells through use of transcription factors normally active in undifferentiated cells
Note: might retain epigenetic memory
Match Hedgehog (Xhh) with its other players
Binds Ptch, activates Smo, activates Gli
Match TGF with other players
TGF + BMP goes with Smad/Co-smad and LOTS of ligands
Match Wnt with other players
Frizlled, beta catenin, Tcf/Lef (prevents beta catenin degradation)
Match FGF with other players
Serine/threonine cascade, Ras
On/off signal (NOT dose-dependent)
