Heads or tails? Stem cells help guide the decision

Two cell embryo

There are many unknown elements for what triggers the cells in an embryo to start dividing and multiplying and becoming every single cell in the body. Now researchers at the Gladstone Institutes in San Francisco have uncovered one of those elements, how embryos determine which cells become the head and which the tail.

In this CIRM-funded study the Gladstone team, led by Dr. Todd McDevitt, discovered almost by chance how the cells align in a heads-to-tail arrangement.

Todd McDevitt

They had created an organoid made from brain cells when they noticed that some of the cells were beginning to gather in an elongated fashion, in the same way that spinal cords do in a developing fetus.

In a news article, Nick Elder, a graduate student at Gladstone and the co-author of the study, published in the journal Development, says this was not what they had anticipated would happen: “Organoids don’t typically have head-tail directionality, and we didn’t originally set out to create an elongating organoid, so the fact that we saw this at all was very surprising.”

Further study enabled the team to identify which molecules were involved in signaling specific genes to switch on and off. These were similar to the process previously identified in developing mouse embryos.

“This is such a critical point in the early development of any organism, so having a new model to observe it and study it in the lab is very exciting,” says McDevitt.

This is not just of academic interest either, it could have real world implications in helping understand what causes miscarriages or birth defects.

“We can use this organoid to get at unresolved human developmental questions in a way that doesn’t involve human embryos,” says Dr. Ashley Libby, another member of the team. “For instance, you could add chemicals or toxins that a pregnant woman might be exposed to, and see how they affect the development of the spinal cord.”

One thought on “Heads or tails? Stem cells help guide the decision

  1. The processes of cellular proliferation and differentiation into a specialized phenotype show a remarkable degree of coordination. That this involves intracellular communication, rather than relying entirely on intracellular programming, was demonstrated nearly 70 years ago by a series of experiments in which the developmental fate of certain regions of xenopus embryo was redirected by the adjacent implantation of tissue originating from other regions. The secretion of growth factor from one cell interacts with target receptor of other cell trigger signal transduction systems which may generate a series of changes in cytoplasmic biochemistry. Thus, growth factors play key role for developmental fate of cell through cell-cell communication.

    All cells produce a variety of growth factor receptors suggests that cell development and behavior in vivo are determined by combinations of interacting stimuli. The target cells for growth factors are characterized by the expression of specific transmembrane receptors that bind the factor and stimulate signal transduction systems which ultimately influence gene expression, proliferation and differentiation decisions. The recruitment of cell into the cell cycle requires the mitogenic response of growth factors. At least, the mixture of two factors stimulate complementary of signal transduction network, both of which are required to trip an essential switch. The potential of synergistic interactions to control developmental processes has been demonstrated in experiments with multipotent precursor cells that can be induced to proliferate and differentiate in vitro in response to combinations of growth factors. For instance, multipotent hemopoietic stem cells do not survive in the presence of either G-CSF or M-CSF in serum-free conditions. The combination of two factors results in a powerful synergistic effect that induced both proliferation and differentiation of the multipotent cells, leading to the development of mature, postmitotic neutrophils and macrophages.

    Stem cells require different stages of maturation to give rise to functionally mature and postmitotic cells. However, their response to specific growth factor changes from one stage to the other stage. This presumably reflects a differentiation-linked change in either the constituents or the ultimate targets of the signal tranduction network. There is qualitatively different results may even arise in a concentration-dependent manner from the action of a growth factor on a specific cell type, as is demonstrated by the chemotactic response of cells to high concentration of growth factor, compared with a mitogenic response to low concentrations. This is explained many growth factors mimic Wnt agonism and threshold amount of agonism may stimulate singular axial extension.

    Growth factors research is critical to characterize growth factor induce each maturation stage of cell development. Different growth factors with critical part of signal transduction network may play important roles in cell functioning and development. These may provide an important clues for clinical development of deformed fetus and effective therapeutic treatment for associated disease. The organoids produced by iPSc technology represent an early culture model with population of less developmentally restricted progenitor cells. The partially development of signalling pathways provide little clue to translate clinical benefit for future medicine.

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