test 2 limbs Flashcards
Outgrowth of the embryonic body wall, consisting of mesenchyme derived from the somites and the lateral plate mesoderm. These precursors accumulate and proliferate under the epidermis to create a bulge called the ____
limb bud
limb buds are formed from ___ and ___
lateral plate mesoderm- somatic mesoderm and the ectoderm
paraxial mesoderm- somites - myotome (muscle of limbs)
___ are muscle precursors and are the only limb component derived from somites rather than somatic lateral plate mesoderm
Migrating hypaxial cells
Migrating hypaxial cells are muscle precursors and are the only limb component derived from ___ rather than ___
somites
somatic lateral plate mesoderm
The mesenchyme of the limb bud is derived from the mesoderm:
somites -hypaxial cells (muscle precursors)
somatic lateral plate mesoderm (skeletal precursors)
what determines where limbs are formed
Hox genes that provide positional information in the developing embryo are good candidates.
mammalian hox genes are ___ to fly hox genes
4 orthologous paralogs in mammals
where does forelimb form
where HoxC6 stops
Where does hind limb form
where HoxC8 stops
what three genes determine limb location
HoxB5, HoxC6, HoxC8
explain why no forelimb in python
HoxC6 starts at top therefore no place where it stops= no forelimbs
HoxC8 goes from top almost all the way down= hindlimbs very far down, residual nubs
these genes are expressed throughout the trunk starting from the hindlimb up to the first cervical vertebrae. A sharp boundary of HOXC8 is detected near the future hindlimb. Expansion of HOXC6 and HOXC8 expression in python embryos can account for extended thorax and loss of fore limbs.
Expansion of ___ and ___ expression in python embryos can account for extended thorax and loss of forelimbs.
HOXC6 HOXC8
A gradient of ___ along the anterior-posterior axis may activate specific combination of Hox genes to specify the limb fields
retinoic acid
Retinoic acids role in limb development
critical for the initiation of limb bud outgrowth.
gradient of retinoic acid along the anterior-posterior axis might activate specific combination of Hox genes in particular cells and specify them to become part of the limb field.
Limb identity may depend on the axial level at which it emerges.
___ is sufficient to trigger limb bud formation.
FGF10
fibroblast growth factor
Local application of FGFs to the anterior flank induces development of a wing, and FGF applied to posterior flank induces a leg. This suggested that limb identity of the additional limb may depend ___
on the axial level at which it emerge.
Ectopic limbs located in the mid-flank appear ___, possessing characteristics of both wings and legs.
chimeric
Hox genes are transcription factors that contain a ___ where Tbox genes are transcription factors that contain a ___
homeobox DNA binding domain
Tbox DNA binding domain
Tbx5 makes ___ where Tbx4 makes ___
forelimb
hindlimb
What gene leads to hind limb?
Tbx4
the expression of Tbox is controlled by FGF 10
Tbox5 inhibits Tbox 4 and works with Hox Code to determine which Tbox is expressed
What gene leads to front limb
Tbx5
the expression of Tbox is controlled by FGF 10
Tbox5 inhibits Tbox 4 and works with Hox Code to determine which Tbox is expressed
Ectopic limbs located in the mid-flank appear chimeric for ___ expression.
Tbx5 and Tbx4
the signal for limb bud formation comes from the lateral plate mesoderm cells secreting ___
FGF10.
which triggers the expression of Tbox 5 or Tbox 4
The early limb bud has two major components -
a core of loose mesenchymal mesoderm cells
an epithelial ectodermal layer
The limb mesenchyme signals (via ___) the overlying ectodermal to elongate and thicken, to form the ___.
FGF10
apical ectodermal ridge (AER)
AER
apical ectodermal ridge (AER)
The ridge of the AER runs along the distal margin of the limb bud.
The factor secreted by the mesenchyme to induce the AER is FGF10.
Outgrowth and differentiation of the limb depend upon inductive interactions between the AER and the underlying limb mesenchyme.
Outgrowth and differentiation of the limb depend upon inductive interactions between the ___ and the underlying limb mesenchyme.
AER
apical ectodermal ridge
The factor secreted by the mesenchyme to induce the AER is ___
FGF10.
Examples of reciprocal signaling between Mesoderm and AER (Ectoderm)
If the AER is removed, the mesoderm stops dividing.
If a supernumerary AER is grafted adjacent to a developing limb, a supernumerary limb results.
If forelimb mesoderm is replaced by hindlimb mesoderm the AER will direct development of the grafted limb into a hindlimb.
If limb bud mesoderm is removed from an early limb bud and replaced by non-limb mesoderm, the AER regresses and the mesoderm ceases proliferation.
Molecules of the FGF family appear to be responsible for the AER activity. If AER is removed and replaced by a bead soaked in FGF a normal limb development will form. ___ is expressed at the right place and the right time to play this role.
FGF8
what are two models to explain limb patterning?
termporally
pre patterned
limb is broken into three zones:
stylopod
zeugopod
autopod
The zone immediately adjacent to the AER is the ___
progress zone (PZ).
The AER is believed to maintain ___ cells in an undifferentiated state, stimulating their division
progress zone (PZ)
AER produces ___ which stimulates the ___ to ___
FGF8
progress zone
to produce differentiated cells, the cells that leave first and differentiate first become the humerus (stylopod) then zeugopod, then autopod
The ___ participate in the establishment of the proximal-distal axis of the limb
progress zone
During outgrowth of the limb, cells of the ___ are assigned progressively more distal positional identities.
progress zone
Cells leaving the progress zone differentiate and their positional value will depend on the time at which they leave the progress zone.
explain
cells that leave PZ first are the cells that will turn into the humerus, closest to the body. will form cartilage and bone before the cells that leave the PZ last that become fingers
The first cells leaving the progress zone form ___ structures, the cells that have undergone numerous divisions in the progress zone become the more ___.
proximal (humerus)
distal structures (fingers)
If AER is removed then ___
limbs will stop developing, if removed early on humerus will form is AER removed later humerus and radius will form ect.
what makes flipper babies
thalidomide
phocomelia
Thalidomide blocks cell growth in the progress zone despite continued exposure to AER-derived FGF8
phocomelia
flipper babies from exposure to thalidomide
Thalidomide blocks cell growth in the progress zone despite continued exposure to AER-derived FGF8
cells in the progress zone never end up outside the range of FGF8. Instead, the entire PZ is progressively assuming distal characteristics. -hand only instead of arms and hands
___ is essential for joints formation and for the separation of the digits.
apoptosis (programmed cell death)
The signal for apoptosis is provided by ___ expressed in the interdigital mesenchyme.
Bone Morphogenetic Proteins (BMPs)
In the duck, cell death is inhibited by a ___, expressed between the digits.
BMP inhibitor, Gremlin,
keeps webbing
Abnormal persistence of soft tissues between the digits or lack of separation of the digits is a condition known as ___
syndactyly.
syndactyly
Abnormal persistence of soft tissues between the digits or lack of separation of the digits is a condition known as
three axes of limb
proximal-distal, anterior-posterior and dorsal-ventral
The AER extends from the anterior to posterior along the dorsal/ventral boundary of the growing limb. Immediately under the AER is the ___.
progress zone
Located in the posterior mesoderm is the___ that controls the ___ polarity of the limb.
ZPA zone of polarizing activity
anterior-posterior
The __ axis is specified by a timing mechanism and the dorsal-ventral axis is specified by the ectoderm. The AER, PZ and ZPA cooperate, so that limb patterning and growth are partly dependent of their coordinated function.
proximal-distal
The ___ axis is specified by the posterior mesoderm of the limb bud known as the zone of polarizing activity (ZPA).
anterior-posterior
The pattern of digit formation is dependent upon the ___.
zone of polarizing activity ZPA
Anterior transplantation of ZPA induces ___ of the digits.
duplication
___, a secreted protein, mediates the polarizing activity of the ZPA.
Sonic hedgehog (Shh)
Why doesn’t FGF8 activate Shh expression in the entire mesenchyme beneath the AER?
only cells in the zone of polarizing activity produce Gremlin. This inhibits BMP. This makes the cells differential competence which allows then to innertact with Shh and activate a FGF4-Shh feedback loop.
In the limb bud the ___ polarity is determined by the ectoderm by ___
dorsal-ventral
palm vs back of hand
Wnt7a
The___ gene is restricted to the dorsal ectoderm of the limb bud.
Wnt7a
is Wnt 7a is removed from limb bud what will happen
no dorsal region
would have palms on both side of hand
how does Sox 9 lead to bone
mesenchyme + sox 9 = cartilage which is then replaced by bone during endochondral ossification
