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20 Cards in this Set
- Front
- Back
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where do limbs emerge on the body?
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forms at the center of a disc of cells called a limb field
limbs develop when mesenchyme cells proliferate from the somatic layer of the limb field lateral plate mesoderm and from the somites at the same level and form a limb bud. position of limb bud is constant with respect to the level of hox gene expression along the anterior-posterior axis the lateral plate mesoderm in the four limb fields induces myoblasts to migrate out from the somites and enter the limb bud to become the limb musculature |
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how is the AER established and maintained
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shoulder-finger axis is made possible by a series of interactions between the AER and the limb bud mesenchyme directly beneath it. the distal mesenchyme is called the progress zone mesenchyme since it proliferative activity extend the limb bud. the AER is induced by fgf10 at the point between the dorsal and ventral ectoderm. fgf10 induces fgf8 in the AER, and fgf8 maintains Fgf10 in mesenchyme. the continued expression of fgfs maintains mitosis in the mesenchyme underneath the AER
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what is the role of hox genes in limb patterning
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specifies whether a particular mesenchymal cell will become stylopod, zeugopod, or autopod and also specifies both the ZPA and the identity of the digits
Hox9 and 10 specify stylopod, hox11 specify zeugopod, and hox12 and hox13 specify autopod. |
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how is the anterior-posterior axis formed?
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a small block of mesoderal tissue near the posterior junction of the young limb bud and the body wall called the zone of polarizing activity, where shh is expressed. the side of the limb bud expressing shh will become the posterior or pinky side of the arm
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how is the dorsal ventral axis formed?
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dorsal-ventral or knuckles-palms
determined by the ectoderm encasing the limb bud. wnt7a gene is expressed in the dorsal ectoderm of limb buds. wnt7a activates lim1 gene in dorsal mesenchyme. lim1 encodes txn factor that specifies dorsal cells fates in the limb |
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how are all the axes coordinated?
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when the limb bud is relatively small, an initial positive feedback loop between Fgf10 and Fgf8 is established. As the limb bud grows, the ZPAis established and anoth-er regulatory loop is created. Sonic hedge-hog in the ZPA activates Gremlin, which inhibits BMPs. The BMPs (mostly BMP4) are able to inhibit the FGFs of the AER. Thus, Sonic hedgehog in the ZPA prevents down-regulation of the FGF genes expressed in the AER: fgf4, fgf8, fgf9, and fgf17. relatively low levels of AER FGFs activate Shh and keep the ZPA functioning. The FGF signals repress the proteins Etv4 and Etv5, which are repressors of Sonic hedgehog transcription. the AER and ZPA mutually support each other through the positive loop of Sonic hedgehog and FGFs. In this phase of limb development, levels of Gremlin ( a powerful BMP antagonist) are high, and the positive FGF/ Shh loop sustains the limb growth. as FGF levels rise, they block Gremlin expression in the distal mesenchyme.
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what is the role ofa cell death in patterning the limb?
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each digit is determined by the interdigital mesoderm (webbing between digits). the interdigital tissue specifies the identity of the digit forming anteriorly to it.
radius and ulna are separated by an interior necrotic zone and the anterior and posterior necrotic zones shape the end of the limb. |
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how do limbs grow
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region of all cells in the area that are capable of forming a limb. any part of this region is capable of generating an entire limb
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limb field
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mesenchymal cells proliferate and accumulate under the ectodermal tissue to create a circular bulge
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limb bud
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what is the signal for initiation of limb bud formation
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Fgf8 is eliminated from areas that will form limb buds due to retinoic acid secreted by somites. where there is no Fgf8 secreted by the somites, paracrine factor Fgf10 is secreted by the lateral plate mesoderm cells that will become the prospective limb skeleton. the signal initiates the limb forming interactions between ectoderm and mesoderm. Fgf10 expression is stabilized by actions of Wnt proteins
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how do you differentiate between fore limbs and hind limbs
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hox genes activate tbx genes
genes encoding tbx4 and pitx1 are expressed in hind limb lateral plate mesoderm gene encoding tbx5 txn factor is found in the anterior lateral plate mesoderm of forelimbs tbx genes activated fgf10 |
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A ridge along the distal margin of the limb bud that will become a major sig-naling center for the developing limb.
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apical ectodermal ridge
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what are the roles of the AER
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(1) maintaining the mesenchyme beneath it in a plastic, proliferating state that enables the lin-ear ( proximal- distal) growth of the limb;
( 2) maintaining the expression of those molecules that generate the ante-rior- posterior axis; and ( 3) interacting with the proteins specifying the anteri-or- posterior and dorsal- ventral axes so that each cell is given instructions on how to differentiate. |
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the limb bud mesenchyme directly beneath the apical ectodermal ridge. the proximal-distal growth and differentiation of the limb bud are made possible by a series of interaction between the AER and this ___.
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progress zone
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how is the proximal-distal axis formed
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positional information for proximal-distal polarity is in the mesenchyme
the limb bud becomes sequentially patterned into three areas. In the first area, basically the progress zone, cells respond to FGFs from the AER that suppress the synthesis of fibronectin and thereby prevent condensation of the mesenchyme cells into car-tilaginous nodules. In the area just beyond the reach of the AER signals, each mesenchymal cell becomes responsive to TGF- ß signals produced by other mesenchymal cells and by themselves. This is the region of patterning activity that directs the formation of cartilaginous nodules. TGF- ß acts ( 1) as a positive inducer of itself, ( 2) as a positive inducer of the extracellular matrix protein fibronectin ( which induces cartilaginous nodule forma-tion), and ( 3) as an inducer of its own soluble inhibitor ( which has not yet been identified). This signaling creates a periodic pattern of regions alternately containing and lacking TGF- ß and fibronectin. the form of each bone depends |
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retion of mesodermal tissue near the posterior juction of the young limb bud and the body wall that maintains polairty of the limb
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zone of polarizing activity
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how is digit identity specified
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sonic hedgehog secreting cells from the zpa do not undergo apoptosis and instead become the bone and muscle of the posterior limb.
specification of the digits is dependent on the amount of time shh is expressed and by the concentration of shh that other cells receive. cells of digit 5 express shh longer and are exposed to shh for longer. digit 3 has some cells that secrete shh for a shorter time than those of digit 4 and depend on shh diffusion from the zpa. digit 2 is dependent on shh diffusion and digit 1 is independent of shh. digit 1 is specified by hoxd13 in the absence of hoxd12. shh works by sustaining a gradient of BMP proteins accross the bud. |
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what is the signal for apoptosis
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bmp proteins are expressed throughout the progress zone mesenchyme but noggin protein supresses BMPs everywhere but in interdigital mesenchyme
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how are joints made
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BMP can be received int he presence of FGFs (to produce apoptosis) or Wnts (to induce bone). when fgfs from the AER are present, Dkk is activated. this protein mediates apoptosis and at the same time inhibits wnt from aiding in skeleton formation
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