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    In mice, the gene encoding Tbx5 is transcribed in limb fields of the forelimbs, while the genes encoding Islet1, Tbx4 and Pitx1 are expressed in presu
    Question

    In mice, the gene encoding Tbx5 is transcribed in limb fields of the forelimbs, while the genes encoding Islet1, Tbx4 and Pitx1 are expressed in presumptive hindlimbs.

    Following statements are made about limb development in mouse:

    A. Loss of Tbx5 gene results in complete failure of forelimb formation.
    B. Hindlimb bud growth and initial patterning appears normal when Tbx4 is knocked out, although leg development is arrested prematurely.
    C. Misexpression of Pitx1 in forelimb causes development of hindlimb-like tendons.
    D. When Islet1 is inactivated specifically in the lateral plate mesoderm, the hindlimbs still develop.

    Which one of the following options represents a combination of correct statements?

    A.

    A and B

    B.

    A and C

    C.

    B and C

    D.

    C and D

    Correct option is A

    Explanation-

    In vertebrates like mice, limb development is tightly regulated by a set of transcription factors and signaling pathways. The key genes involved here are:
                                                                                Tbx5 – essential for forelimb (arm) development
                                                                                Tbx4 – crucial for hindlimb (leg) development
                                                                                Pitx1 – determines hindlimb identity, upstream of Tbx4
                                                                                Islet1 (Isl1) – required for the initiation of hindlimb bud formation

    Option a - Loss of Tbx5 gene results in complete failure of forelimb formation.      -  True
    Tbx5 is expressed specifically in forelimb-forming regions of the lateral plate mesoderm. It activates the FGF10–FGF8 loop required for limb bud formation. If Tbx5 is knocked out, mice fail to form forelimb buds at all.

    Option b -  Hindlimb bud growth and initial patterning appears normal when Tbx4 is knocked out, although leg development is arrested prematurely            - True
    Tbx4 is required for further differentiation and morphogenesis of the hindlimb. Early stages like hindlimb bud initiation and patterning can occur via Pitx1, which is upstream of Tbx4. However, without Tbx4, the hindlimbs cannot proceed to form fully developed legs (bones, muscles, etc.).

    Option c - Misexpression of Pitx1 in forelimb ceases development of muscles, bones and tendons.                  -   False
    Pitx1 is normally restricted to hindlimbs and is responsible for giving hindlimb identity. If you force Pitx1 expression in forelimbs, it doesn’t stop limb development—instead, it causes the forelimb to acquire hindlimb-like features.
    For example, skeletal elements in the arm may start to resemble those of the leg.

    Option d -  When Islet1 is inactivated specifically in the lateral plate mesoderm, the hindlimbs still develop.               - False
    Islet1 (Isl1) is essential in the lateral plate mesoderm for initiating hindlimb bud outgrowth. If Isl1 is deleted in this region, the signaling needed to initiate hindlimb formation (e.g., FGF10 signaling) fails, and hindlimbs do not form.

    Correct Statements - A and B
    So, the correct answer is option a : A and B

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