Developmental biologists did the following experiments to discover the role of e
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Question
Developmental biologists did the following experiments to discover the role of endoderm in the specification of cardiogenic mesoderm.
Using early mouse embryos:
Experiment 1: Removed the anterior endoderm and cultured the embryo – no cardiogenic mesoderm and no heart muscle cells developed.
Experiment 2: Removed anterior endoderm and replaced it posterior endoderm from another embryo and cultured the embryo – no cardiogenic mesoderm and no heart muscle cells formed.
Experiment 3: Removed anterior endoderm and replaced it anterior endoderm from another embryo and cultured the embryo – cardiogenic mesoderm and heart muscle cells developed.
Interpret these data. What are the signals that come from the anterior endoderm? What is their role in specification of the cardiogenic mesoderm?
Explanation / Answer
The mouse embryo-like mammals undergoes anterior posterior axis formation. This is brought about by two signaling centers, one in the node and another in the anterior visceral endoderm (AVE)
The AVE secretes two antagonists of the Nodal protein, Lefty-1 and Cerberus (Lefty-1 binds to the Nodal's receptors and blocks Nodal binding, and Cerberus binds to Nodal itself.) Thus there is a gradient of Nodal from anterior end (very less ) to the posterior end (high concentrations leading to mesoderm formation).
The head region (anterior ) of the mammalian embryo is devoid of Nodal signaling, and BMPs, FGFs, and Wnts are also inhibited. The posterior region is characterized by Nodal, BMPs, Wnts, FGFs, and retinoic acid. There is a gradient of VVnt, BMF, and FGF proteins that is highest in the posterior and that drops off strongly near the anterior region.
In experiment 1: no mesoderm was formed because a functional anterior endoderm is required to generate a gradient for nodal signaling.
In experiment 2: posterior endoderm similarly could not secrete the antagonists required to ensure that a proper nodal gradient is formed such that there is no active nodal in the anterior region and plenty of it in th posterior region.
Experiment 3: This proves that anterior endoderm is solely responsible for the generation of gradient that defines anterior-posterior axis. This step is mandatory for the specification of mesoderm.
The gradient of morphogens induces the formation of cardiogenic mesoderm by initiation of several signaling pathways mediated by several transcription factors.
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