Term
stylopod zeugopod autopod |
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Definition
stylopod- humerus/femur zeugopod- radius-ulna/tibia-fibula autopod- tarsals/metatarsals |
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Term
Patterning along which 3 axes? |
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Definition
dorsal-ventral = palm-knuckles anterior-posterior = thumb-pinkie proximal-distal= shoulder-finger/hip-toe |
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Term
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Definition
limb field = precise location at which limb forms - "free limb" + peripheral tissues = limb field - peripheral tissues = shoulder girdle/peribrachial tissues *tissues can be removed without defects --> all tissues in area can form limb* |
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Term
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Definition
limb bud= def. somatic lat. plate mesoderm/somitic mesenchymal cells accumulate under ectoderm to create CIRCULAR BULGE
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Term
LIMB BUDS COMPRISED OF TWO TYPES OF TISSUES |
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Definition
1) somatic mesoderm of lateral plate (skeletal elements) 2) abaxial myotome cells from somite(muscle elements) |
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Term
Compensatory powers of limb buds/fields |
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Definition
- when limb field first forms, any 1/2 of limb disk can form new desk -if grafted to new site, supernumerary limbs will form - if field is split (border b/w split regions), multiple limbs will sprout at site |
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Term
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Definition
-4 limb buds -2 pairs positioned opposite each other (across midline) - pos. adjacent to specific somites -placement of limb buds differs with respect to somite level in different species, but POSITION IS CONSTANT WITH RESPECT TO HOX EXPRESSION - forelimb bund at anterior region of Hoxc6 gene |
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Term
Early limb bud formation- Fgf10 |
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Definition
-earliest stages of bud formation caused by restriction of Fgf10 expression - first expressed throughout lat. plate mesoderm, but prior to limb formation, restricted to region where limb will form -restricted by Wnt Expression - Wntc8 in hindlimb - Wnt2B in forelimb
-Fgf10 initiates limb development along the flank --> initiates interactions between ecto/mesoderm *if Fgf10 beads places under ectoderm, ectopic limbs WILL form! |
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Term
Fgf10 patterning in limb field (cont'd) |
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Definition
- stabilized Fgf10 in lat. plate mesoderm will signal ectoderm to make Wnt3A - Wnt3A drives Fgf8 expression -Fgf8 drives Fgf10 production -FEEDBACK LOOP TO KEEP FGF10 STABLE IN PLATE MESODERN |
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Term
SPECIFICATION OF LIMBS (FORE- VS. HIND-LIMB) |
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Definition
- specification of fore-/hindlimbs through Tbx expression (TFs) - Tbx5 in forelimb - Tbx4 in hindlimb -specification (via Tbx) occurs BEFORE Fgf (Fgfs drive limb formation) expression occurs ... limbs already specified once they begin to form - structure of supernumerary limbs dependant on which Tbx field they are closer to *chick made to express Tbx4 --> anterior limbs became legs instead of wings* |
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Term
Apical Ectodermal Ridge (AER) |
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Definition
-Fgf10 from mesenchyme(lat. plate mesoderm) causes overlying ectoderm to form AER *interaction between adjacent mesoderm and AER critical* - keeps distal mesenchyme (PROGRESS ZONE) proliferative -AER directs growth and patterning of the limb by: (1)maintaining expression of molecule that gen. A-P axis (2) interacting with proteins specifying the A-P/D-V axes |
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Term
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Definition
- if AER is removed, growth of limb stops
- if extra AER, distal structures are formed
- limb is regionally specified by mesenchyme
- if leg mesenchyme is placed just under AE at forelimb height, toes will form on wings
4. if non-limb mesenchyme placed beneath AER, the AER degenerates and growth stops |
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Term
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Definition
- FGFs needs for maintenance and induction of AER
- FG10 from mesenchyme induces formation of FGF8 in the ectoderm of AER
- positive feedback
- FGF10 --> Wnt3A --> FGF8 --> FGF10...
- feedback process keeps mesenchymal cells proliferative so limb lengthens proximal to distal
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Term
P-D Polarity and Specification |
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Definition
- does AER or mesenchyme specify structural polarity of the limb?
- If AER removed at different times, then development stops at different lengths
- **AER does not specify structure--> MESENCHYME DOES**
- ***switching older AER for newer doesn't induce distal structures earlier
- IF progress zone (mesenchymal) of early stage embryo placed on a late stage embryo, P-D duplication
- IF PZ (mesenchymal) of late stage placed on early embryo, distal structures form immediately
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Term
Mesenchymal Specification 2 models: (1) Time - Progress Zone Model (2) Space- Early Allocation and Progenator Expansion model |
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Definition
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Term
(1) Time Model - explains mesenchymal specification |
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Definition
- determined by HOW LONG (i.e. time) cell remains in proliferative PZ
- PZ stays same size even though cells in region very mitotically active--> b/c cells constantly move out of region
- cells that leave cause limb to lengthen
- **the longer a celll state and te more mitosis it undergoes, the more distal a structure it forms**
- removal of the AER stops the clock so only proximal structures form
Arguments AGAINST theory: - when marked with dyes, progeny of cells limited to particular segment of the limb
- time spent in PZ did not specify cell position --> specification earlier!!!!
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Term
2. Space model of mesenchymal specification - Early Allocation and Progenatory Expansion Model |
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Definition
- all the cells in the limb SPECIFIED EARLY
- subsequent divisions expand specified regions
- stratified within the bud
- AER drives proliferation, allows for expansion and survival of progenators
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Term
Hox expression in Proximal-Distal Axis |
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Definition
- Hox proteins are MOLECULAR DRIVERS OF STRUCTURE
- HoxA-D prominent in FORELIMBS
- Hox9/10 in stylopod
- Hox11 in zeugopod
- Hox12/13 in autopod
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Term
Homozygous mutation in Hox(A/D)13 protein |
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Definition
- supports Hox expression theory that Hox genes specify structure
- Hox13 mutuation= distal autopod defects (polysyndactaly)
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Term
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Definition
- Hox11 KO: stylopod forms, zeugopod does not
- Hox10 KO: no femur, patella, etc.
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Term
Zone of Polarizing Activity (ZPA) |
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Definition
- location: @ posterior juncture b/w limb bud and body wall
- transplation of ZPA from posterior to anterior reverses polarity --> result? mirror image duplication of digits
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Term
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Definition
Shh!!!! - defines ZPA
- necessary/sufficient for polarizing activity
- cells that artificially secrete Sh can duplicate transplanted ZPA
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Term
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Definition
- ZPA definition by Shh confirmed with Hx mutation
- Hx mutuation = naturally occurring mouse mutation, hemimelic extra toes
- mirror image duplication of digits
- tracked to a point mutation in the Shh Limb specific enhancer region (upstream from Shh gene)
- Allows for aberrant transcription in anterior regions
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Term
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Definition
- cells secreting Shh incorporated into final limb structure --> become bone,muscle, skin of posterior limb
- don't die like the AER cells (i.e. don't undergo apoptosis)
- muscle, bone,skin of digits 4 & 5 came from Shh secreting cells
- polarity determined by how long Shh was expressed vs. concentration seen by a cell
- autocrine signaling
- digit 5 expresses Shh longer than digit 4
- Digit 3 some Shh expression and a lower gradient signal caused by diffusion of Shh from ZPA
- Digit 2 sees only Shh coming from gradient in ZPA
- digit 1 specified independant of Shh
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Term
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Definition
- DIRECTED BY THE WEBBING BETWEEN THE DIGITS BEFORE IT IS REMOVED
- BMP-mediated
- ***BMP gradient driven by Shh***
- webbing gives identity to digit forming anteriorly to it
- change ID if remove webbig
- change ID if alter BMP expression/signaling
- Noggin-overexpression inhibits BMP
- Noggin overexpression b/w 3 and 4: 3rd transformed anteriorly to digit 2
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