Study Questions 8, Starting from Lecture 15 1. Define proximal-distal, anterior-posterior and dorsal-ventral limb axis. There are three axes 1. Proximal-Distal: Consists of three segments a. Stylopod: most proximal b. Zeugopod c. Autopod: most distal The cartilage is replaced by bone, in the above order. 2. Anterior-Posterior: Using the hand as a reference tool Anterior: the thumb Posterior: the Pinky 3. Dorsal-Ventral Axis: Using the hand as a reference tool Dorsal: Nails and knuckles Ventral: Palm 2.Is the following statement true or false: Wnt proteins stimulate the degradation of Fgf10 in the lateral plate mesoderm, thereby initiating limb bud formation? Explain your reasoning.FGF10 secreted by the lateral plate mesoderm is responsible for inducting asignal for limb formation. Wnt protein does in fact inhibit FGF10 in the lateral plate mesoderm restricting sites of limb bud formation. For instance, Wnt 2b is responsible for restricting the forelimb area and Wnt 8c is responsible for the hindlimb area. Wnt/FGF10 signal feedback on Tbx5and Tbx4to maintain their expression – this is what specifies the limb buds as forelimb or hindlimb. FGF10 in turn activates Wnt3a/3/FGF8 signals in the limb ectoderm, thus, inducing the formation of the apical ectodermal ridge.
3.Describe the roles of Fgf10, Fgf8, Wnt2b, Wnt8c and Wnt3a in the initiation of the chicken limb bud formation. How the above molecules interact with each other to signal the formation of the limb budFGF10, secreted by the lateral plate mesoderm is what induces the limb budformation. Limb bud formation is localized by wnt 2b and wnt 8c. wnt 2b isresponsible for restricting FGF10 to the forelimb bud formation, whereas, wnt 8c is responsible for restricting FGF10 to the hindlimb. This localized expression of FGF10 regulates expression of FGF8/Wnt3a/3 in the ectoderm of the limb bud’s areas. Wnt3a/3/FGF8 induces the formation of the apical ectodermal ridge (AER). 4. Describe the roles of FGFs, Tbx5 and Tbx4 during limb bud formation in the chick. Outline the experiments which demonstrated the roles of the above proteins. In the lateral plate mesoderm, Tbx4 and Tbx5 is responsible for determining where limb bud formation occurs. They essentially initiate Wnt 2b/FGF10 (forelimb specification) & 8c/FGf10 (hindlimb formation). These Wnt/FGF signals maintain their expression. this localization of the FGG induces the overlying ectoderm to form the apical ectodermal ridge. apical ectodermal ridge functions as the major organizing center In birds: gain of function experiments - using beads soaked with FGF 10 Humans heterozygous for Tbx5 have Holt-Oram syndrome, characterized by abnormalities of the heart and upper limbs . Legs unaffected Induction with FGF containing bead at site between normal limbs (gain of function). Induces chimeric limb.
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- Summer '14
- Developmental Biology, Sex-determination system, apical ectodermal ridge, Limb Bud, limb development