Concept explainers
To review:
Whether the hindlimb bud formation is autonomous or nonautonomous. Whether Hox and Islet1 gene expression supports the autonomous mechanism of hindlimb bud expression. Also explain the importance of time in influencing the hindlimb development.
Introduction:
The transcriptional basis of hindlimb bud formation is a well studied system, in relation to organogenesis. A number of signaling molecules regulates this process. The initiation of the vertebrate limbs involves the proliferation of lateral plate mesoderm (LPM), this proliferation initiate outgrowth with a signaling pathway from the LPM to ectoderm. The expression pattern of different genes and gene knockout mutations reveals and specify the identity of a limb region.
Explanation of Solution
In both forelimb and hindlimb bud formation, the fibroblast growth factor 10 (Fgf10) in the LPM activates the expression of another Fgf gene that is Fgf8, in the surface ectoderm. This expression maintains the formation of a mesenchymal Fgf10-ectodermal Fgf8 feedback loop to regulate the limb outgrowth. The genetic mechanism for the hindlimb initiation is still elusive in contrast with forelimb initiation. The two transcription factors Tbx4 and Pitx1 genes are highly expressed in the hindlimb field, but this expression is absent in forelimb field. But the experiment based on gene targeting indicates that neither is necessary for initiation of the hindlimb bud. There is a lack of data on the transcriptional regulation of hindlimb-specific initiation, compared to forelimb, where Tbx5 acts as transcriptional regulator.
Based on recent studies one important transcription factor gene Islet1, is found to be transiently expressed in the hindlimb field, but not in the forelimb field. Further lineage analysis indicates that Islet1-expressing cells forms a large part of the hindlimb mesenchyme. These analyses show Islet1, as a strong candidate to be a hindlimb-specific transcriptional regulator. Tbx4 expression is critical in the specification of hindlimb, just like the role played by Tbx5 in specification of forelimb. The limb field is also specified by the expression pattern of Hox gene. The activity of the limb bud also stimulates the creation and positive feedback retention of two signaling regions: the AER and its further creation of the zone of polarizing activity (ZPA) with the mesenchymal cells. Thus it can be assumed that signaling system critically control the temporospatial hindlimb formation, which are considered autonomous.
Thus it is concluded that a number of signaling molecules shows the critically regulated expression of different guidance hues for the hindlimb bud initiation, which are considered autonomous.
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Chapter 19 Solutions
Developmental Biology
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