Cienciaes.com: How are limbs formed in the embryo? We speak with Irene Delgado Carceller.

2020-08-01 21:06:39

Both we and everyone around us share the same body schema: head up, two arms at the sides at the top, two legs, a pair of eyes, etc. We are so accustomed to observing this scheme that we are only surprised by a person who, due to natural causes or by accident, suffers from some defect or malformation. However, if we go back to the moment of our gestation, when we have a single cell as a starting point, the development of this whole body scheme, so exquisitely ordered, is fascinating.

Imagine that we want to create a human being out of nothing. Before starting we should have a scheme, a sketch in which the different morphological characteristics appear, with each detail and each one in its place: The head at the highest, symmetrical, with the ears on both sides, the eyes on the sides of the nose centered next to the mouth, teeth, arms, legs, etc. Any child knows how to draw it and no one thinks of putting their feet on their heads or their mouths at the level of their navel, except surrealism artists. In other words, we need to have a mental scheme of the position of each member and organ or, otherwise, we may find ourselves with unreassuring aberrations.

However, the process of creation by nature of a human being, or of any animal, follows a very different process. The starting point is a single cell that begins to divide over and over again. The first group of cells thus formed shows no signs indicating the existence of the schema of a fully formed person. It is later in the development process that cells begin to differentiate to generate the various limbs and organs.

Let’s take the development of an arm as an example. At a given moment, the embryo must know where a bulge should appear, the primordium, from which the arm, elbow, forearm and hand will be generated, each piece in its place. It is as if an engineer were indicating to the cells the exact position of each piece. But there is no such engineer, the appearance of the various parts, in their exact order, is due to a complex set of molecular and genetic interactions that have long been the subject of research. Now, a group of researchers from the National Center for Cardiovascular Research (CNC) has identified a system that provides information to the cells of the embryo about the position they occupy in the limbs during development. The results have been published in an article in Science Advances, whose first author is Irene Delgado Carceller, our guest today in Speaking with Scientists.

When a limb begins to form, the first step is to generate the “primordium”, a bulge of cells from which the different components are generated. Thus, the primordium from which an arm will emerge will generate, at different distances from the origin, the forearm, the elbow, the arm and the hand. Researchers have been able to decipher how the cells obtain the information that tells them where they are on the axis that goes from the positions closest to the shoulder (proximal) to those furthest away (distal).

Irene Delgado explains how her team has identified a growth factor, called FGF, which is the molecular signal that cells receive to interpret their position. The signaling molecules of this factor FGF, are produced and sent to the extracellular medium by only a small group of cells in the most distal or remote part of the primordium. The concentration differences of FGF indicate the closeness or distance of the cells, that is, the further away the cell is, the greater the amount of FGF which receives, on the other hand, if the position is closer, the amount of FGF it will be smaller.

The concentration of FGFwhich varies as a function of distance, is interpreted as a signal inside each cell by a transcription factor, called Meis, , such that the amount of Meis that exists inside the cell reflects how much FGF there are abroad. Transcription factors can regulate the functioning of the genome, that is, they can turn genes on and off, allowing cells to specialize and become part of the corresponding region. Thus, the cells that receive the information that they are in a more proximal place will activate the genes that allow them to generate the part of the arm attached to the shoulder, while those located at greater distances will receive the orders to form the elbow, forearm and hand. .

When the training system does not work correctly, malformations such as phocomelia can occur, a congenital anomaly that develops only the hands and feet while the rest of the extremity is rudimentary.

I invite you to listen to Irene Delgado Carceller, a researcher at the Cardiovascular Development Program of the National Center for Cardiovascular Research (CNC)

Reference:
Delgado et al.: Proximo-distal positional information encoded by an Fgf-regulated gradient of homeodomain transcription factors in the vertebrate limb. Sci. Adv. 2020; 6 : eaaz0742