Magic embryology: sculpting a new heart (Introduction)

by David Turell , Thursday, March 30, 2023, 19:10 (605 days ago) @ David Turell

Defining the molecular agents in charge:

https://phys.org/news/2023-03-key-mechanism-human-heart.html

"In humans, a specialized mRNA translation circuit predetermines the competence for heart formation at an early stage of embryonic development, a research team at the Center for Molecular Medicine Cologne...discovered.

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"They found that the protein RBPMS (RNA-binding protein with multiple splicing) is responsible for the decision to make the heart by programming mRNA translation to approve future cardiac fate choice.

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"Since the heart is the first functional organ to form in a developing embryo, any anomaly in early embryonic cell fate decisions needed for the development of the heart leads to catastrophic consequences, often resulting in the termination of pregnancy or lifelong suffering due to congenital heart diseases.

"In humans, approximately 30 percent of developing embryos terminate before implantation in the uterus, and about 25 percent fail during the transition from gastrulation (the early phase when the embryo begins to differentiate distinct cell lineages) to organogenesis (the phase that lasts until birth when all tissues and organs form and mature).

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"The team discovered that the competence for the future cardiac fate is preset in human embryonic stem cells (hESCs) by a specialized mRNA translation circuit controlled by the RNA binding protein RBPMS. RBPMS is recruited to active ribosomes, the molecular machine that produces proteins from mRNA. There, RBPMS controls the production of essential factors needed for the program that triggers the stem cells to develop into heart cells.

"Mechanistically, RBPMS has two functions. On the one hand, the protein interacts with components to promote the translation of mRNA to proteins; on the other hand, RBPMS selectively regulates the production of mesoderm signaling components in hESCs by binding to a specific site on the mRNA. The mesoderm is the middle layer of the three germ layers, from which the heart develops early on in embryos.

"It is believed that through early contact with cardiogenic signals, the ability of stem cells to develop into future cardiac lineages is predetermined. This study shows that the RBPMS-mediated selective mRNA translation circuit approves the cellular abundance of 'morphogen signaling infrastructure' required for cardiac mesoderm approval in hESCs. Thus, RBPMS sets up the future cardiac competence of hESCs by programming selective mRNA translation. (my bold)

"'In summary, we present a model whereby the state of pluripotency is primed for differentiation into future cell lineages through specialized translation of the regulators of embryonic cell fate. Our work shows that RBPMS selectively programs translation, i.e. the reading of mRNA and the production of proteins or mRNAs. This controls proteins and regulatory mRNAs that themselves code for important developmental regulators and are essential for deciding future cell fate," Dr. Deniz Bartsch, first author of the study, explained.

"Based on their findings, the team proposes 'translation specialization': a regulatory mechanism that primes ribosomes to control translation in time and/or space for a set of mRNAs required for future events in response to specific stimuli or fate transitions. This allows efficient division of labor among the approximately ten million ribosomes present in each cell, which are tasked with synthesizing about two million proteins per minute, so the flow of information is streamlined and, as they show, specialized. (my bold)

"This study, therefore, reveals a central role for translational specialization in shaping cell identity during early lineage development and proposes that ribosomes act as a unifying hub for cellular decision-making rather than a mere protein factory."

Comment: these actions follow the information in the stem cell genome. T his complexity did not come from chance mutations. Darwin theory has no explanation.