How to Build a Human: Adventures in How We Are Made and Who We Are. Philip Ball

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       Gradients in the concentration of proteins bicoid and caudal from opposite ends of the fruit-fly embryo switch on genes at different positions that cause segmentation of the body plan.

      Other diffusing morphogens produce other kinds of gradient, defining different axes of the emerging body. For example, a protein called dorsal is involved in setting up the top-to-bottom (dorsoventral) axis of the fruit-fly embryo that distinguishes the region that will become the back (where the larva will ultimately grow wings) from that which will become the belly. In each case, the gradient thresholds may turn particular genes on and off in a series of elaborations that begins with the crudest determinants of shape – the front/back and top/bottom axes, say – and works its way to the fine details.

      The idea that chemical concentration gradients might control the development of embryos was first proposed at the start of the twentieth century by Theodor Boveri. By producing a chemical patterning signal that spreads into the rest of the embryo, one cell can determine the fate of other cells nearby. In 1924 Hans Spemann, together with Hilde Mangold, called such groups of cells “organizers”.¹⁰ Mangold transplanted groups of cells in amphibian embryos from one position to another and saw that they could induce the development of “out of place” features.

      The British biologists Julian Huxley and Gavin de Beer verified the idea of organizers in the 1930s by manipulating the embryos of birds. They proposed that Spemann’s organizers create “developmental fields” of some kind that influence the course of development. Spemann had imagined this “field” as something like the magnetic or electrical fields of physics, but Huxley, de Beer and their contemporaries in this fledgling field of developmental biology suspected that the agent was a chemical one. The notion that these organizing centres define a sense of position within the emerging body plan through the action of morphogen concentration gradients was crystallized in the late 1960s by biologist Lewis Wolpert.

      There’s a crucial part of this story that I’ve skipped over so far. The patterning of the fruit-fly embryo is kicked off by the production of the bicoid protein at the anterior tip of the egg. But what causes that production in the first place? How does the bicoid gene know it is at the anterior end?

      The answer is that “mother tells it”. While the unfertilized egg is attached to the follicle of the mother fly, specialized cells called nurse cells deposit material needed to make bicoid – specifically, the RNA molecules that mediate the gene-to-protein conversion – into the anterior tip of the egg, so that developmental patterning is all ready to go when the egg is fertilized. Right from the outset, cells in the embryo are dependent on other cells around it to know what to do. It’s for similar reasons that a fertilized human egg can’t develop fully in isolation, if cultured in a test-tube. Implantation in the uterus wall is needed to give it a “sense of up and down”. Ectopic pregancies (within the fallopian tubes) show that such a signal doesn’t have to come from the uterus, however, and we’ll see later whether there might be other ways to do produce it in vitro.

      This is why it is strictly incorrect to say – although it often is said – that all the information needed to grow a human being is in the genome of the fertilized egg, which is in turn supplied by the gametes that combined to make it. You could say that the human embryo also needs positional information supplied by its environment – specifically by the uterus lining. Furthermore, any particular cell in the developing embryo depends on receiving information from the surrounding cells in order to keep embryo growth on track. As the transplantation experiments of Huxley and de Beer showed, if you mess with that information then you screw up development, despite the fact that every cell retains its complete “genetic programme”.

      Embryo development is thus not encoded from the outset in the genome, as if in some blueprint or instruction book. It relies on a precise expression of genetic information in time and space, which in turn depends on the proper coordination of many cells (including maternal ones) and is subject to chance events during the execution. To understand embryology and the growth of complex tissues and organisms, we shouldn’t imagine that we will find a set of instructions packed like a homunculus inside the zygote. Rather, we will need to discern and interpret the patterns of information flow (and the various sources of that information) as the process unfolds.

      It’s rather as if the genome is a list of the words that feature in a book, but you need other information to put the words in the right order so that they become more than just assemblages of letters and may take on meanings. Those meanings are not inherent in the words themselves but may be determined by the words nearby, by allusions and interactions that leap from one part of the text to another – by context. Again, there is no perfect metaphor for illustrating how genes work in building an organism; doubtless this one would collapse too under pressure, so use it gently.

      * * *

      I won’t explain in detail how human embryogenesis differs from that of the fruit fly, but it’s worth understanding one of the most basic distinctions. For the human body doesn’t simply emerge imprinted on the inner cell mass of the blastocyst like stripes on an embryonic zebra.¹¹ Rather, the cells in the embryo move around, and the tissues grow, buckle and fold, to shape the body. It’s a highly active process, a kind of auto-origami happening in parallel with the appearance of distinctions between cell types. The first stage of this process, which for humans occurs around day 14 after fertilization (around the time that a pregnant woman might first notice a missing menstrual period), is called gastrulation. Some scientists regard this as the point where a mass of cells begins to produce an organism: as the beginning of personhood.

      There is a lame joke that scientists still seem to find amusing about how, if a physicist were to study the cow, she would first simplify the question by approximating it as a sphere. It is rendered all the lamer by the fact that this is not so far from how nature approximates the human body – or the bovine one for that matter – in the first instance. For the most rudimentary idealization of our body might run thus: an inner tube for digestion from mouth to gut to anus, an outer layer of skin to create a boundary, and everything else packed into the space in between. At one end we’ll put the head – the anterior – and at the other end is of course the posterior. Gastrulation creates a structure very much like this (the word actually means “gut formation”). In some creatures, such as species of worms and molluscs, it really is that simple: gastrulation folds the embryo into a sort of fat tube or doughnut shape in which an inner tube connects mouth to anus, and the job is nearly done at a stroke.

      For humans, it is rather more complicated. The embryo СКАЧАТЬ