Positional Information – Embryology

by John McLachlan, PhD

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    00:01 Once the cells are formed in the inner cell mass, if we now look at our little blastocyst, here again, you can see that all the trophoblast cells, some of them are in contact with the inner cell mass and some of them are not. So the next step would be that the ones in contact with the inner cell mass will specialize in a different way from those which are not in contact. Similarly if you look at the inner cell mass cells, some of them are exposed to the space in the center to the coelom to the opening in the middle of the blastocyst and some of them are in contact with trophoblast cells and again these will have different fates. So we went from one cell kind to two cell kinds. Those two cell kinds now generate four cell kinds. We are looking at a cascade of differentiation following from these developmental signals, which are transmitted from cell to cell. So different fates comes as a result of different positions and although we do not fully understand the nature of all those signals, we are understanding some of them and this is a work very much in progress.

    01:10 So here you can see in the diagram, trophoblast cells not in contact with the inner cell mass all follow a different fate from those in direct contact, inner cell mass cells are exposed to the blastocyst will follow different fate from those that are not exposed to the blastocyst. The idea behind this is called positional information by Prof. Lewis Wolpert.

    01:32 And a good way to help to understand this is to look out the development of the fruit fly.

    01:36 Now first you may think that the fruit flies are a long way from human beings even in this idealized view, it does not look much like a person. But what we now know is that the developmental signals and the developmental genes, which help express different parts of the embryo during the course of development are actually common to all animals and indeed common to animals and plants in many cases as well as if there is one set of developmental genes which are activated at different times in the development of all living things and it is fair to say that this was a very unexpected finding indeed. And this is despite the fact that the different part of an organism can be very varied between different species.

    02:24 So for instance the eye of a fly is very different from the eye of a human, but the underlying genes to say make an eye, turn out to be almost identical. Same would be true of heart formation for instance; aspects of brain formation, aspects of the genital apparatus and aspects of the limbs despite the fact that they vary from animal to animal. The developmental signal that says form a limb, turns out to be very similar. And if you want to know more about this, then Hox genes would be a great starting place to gather more information. But I can give you one example. There is a mutation found in fruit flies called "eyeless" and what that does is to affect eye development, as you might have guessed and because it is easy to breed fruit flies and analyze their genetics, we can identify the gene that is involved in this 'the eyeless gene'. The particular gene involved is known as Pax 6 and if you look at the human genome, you will find the gene very similar to Pax 6 in its structure and from time to time children are born with eye defects, a common one is the reduction in the size of the eye and because we know the nature of Pax 6 in fruit flies, we can explore the human genome for a corresponding gene and we find one and what we know is that if you are to remove that gene from a human and to place it in a developing fly, it would restore eye formation in that fly. Now you might be wondering will that extra eye be a human eye or a fly eye and perhaps disappointingly is the fly eye. The signal coming from Pax gene tells the fly to make an eye, but the fly interprets that signal in the light of its evolutionary history and therefore it makes a fly eye. If you can do the converse experiment, take that gene from a fruit fly and then planted into a human would be illegal, but technically it would be possible. Then an eye created by that gene would be a human eye and not a fly eye. And this, of course, is a very good way of looking for the genes that underlie developmental defects in humans. If we found, for instance, a heart defect in humans, we could rapidly scan the fruit fly to find a gene that caused heart mutations in the fly and then check to see that if that gene was altered or abnormal in the human that were suffering from that heart condition. Again if you want to know more about this, the Pax genes would be the thing to look up. Now I have posed a very startling question

    About the Lecture

    The lecture Positional Information – Embryology by John McLachlan, PhD is from the course Embryology: Early Stages with John McLachlan.

    Author of lecture Positional Information – Embryology

     John McLachlan, PhD

    John McLachlan, PhD

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