Life Unfolding

Life Unfolding
Author: Jamie A. Davies

Background

With an awe-inspiring narrative, this book explores the processes by which ‘small, simple molecules‘, without any ‘prior plans‘, and without any central controlling mechanism, achieve the amazing feat of transforming a single-celled embryo into a fully functional human. At the heart of the book is the phenomenal concept of self-organisation, the intricate and sophisticated mechanism that uses ‘relatively simple, local rules‘ to drive embryogenesis. The book succeeds in painting a graphic picture of the diverse and elaborately complex operations that take place at multiple sites, and at different times during foetal development, that enable an independent sentient being to emerge from a seemingly chaotic cacophony of mindless activity. Rather than a dry portrayal of physical changes, the book’s strength lies partly in its exploration of the genetic mechanisms that underlie early human development, for example how sonic hedgehog and noggin govern the maturation of the cardiovascular and blood systems. Similarly, beyond just depicting the normal process of foetal development, the book also covers the pathology that emerges when the process goes awry, as reflected in its discussion of the neurocristopathies – nerve cell migration disorders such as Hirschsprung, Waardenburg, and Treacher-Collins (pages 18, 5, 7, 64, 103 and 109-121).

By Database Center for Life Science (DBCLS), CC BY 3.0, Link

Synopsis

The process of cell division, key to all stages of embryogenesis, is at the centre of this book. In describing this important mechanism, the author portrayed the protein tubulin as ‘the star of the show‘. In what can only be portrayed as a remarkable performance, the book depicted the staggering contortions of tubulin as it assembles to form microtubules –  the structures which will then extend outwards ‘like spokes from a hub’, towards two opposite ends of the cell. These microtubules, the author pointed out, are necessary for exerting the pulling and pushing forces which enable their centrosomes to ‘take up positions about half way between the real centre of the cell and the edge’, a step necessary to ensure an equal division of the cell’s contents. The author also chronicled the similar self-organising way by which the microtubules, before the cell starts to divide, bind and pull the chromosomes ‘to the centre of one of the daughter cells‘. Typical of all great shows, the denouement of cell division is climatic, demonstrating as it does the eventual dramatic cleaving of the cell under the influence of ‘further automatic systems’ of proteins which ‘contract until the cell is finally split completely into two new cells’. The author emphasised that this unbelievable feat, like all the other operations of embryogenesis, is achieved without any obvious central coordinating system (pages 20-26).

Chromosomes (blue) lined up for cell division. ZEISS Microscopy on Flickr. https://www.flickr.com/photos/zeissmicro/14256070350

The process which perhaps best symbolises the dominance of local factors over foetal development is that of cell specialisation, the mechanism by which ‘a collection of initially identical cells will lose its homogeneity‘, with each cell going on to become a completely different tissue or organ. In describing how this otherwise improbable transition relies completely on ‘purely local influences‘, the author stressed that there is no single cell directing the performance, and none is cognisant of ‘the big picture‘. The book pointed out that the key concepts governing cell specialisation, fundamental to the overall metamorphosis that is embryology, are ‘the breaking of sameness‘ and ‘the establishment of differences‘. Indeed these two process are reflected in the illustrative examples the author provided, for example the way the trophoblast will transform into the placenta, and how the inner cell mass will differentiate into the epiblast – the ‘source of all of the cells in the baby‘. A rather different form of tissue specialisation the book also reviewed, and which dominates in the later stages of foetal development, is that of ‘elective cell death‘ – the mechanism that governs the fashioning of the hands and feet, the elimination of two extra pairs of kidneys, and the pruning of motor neurones in the nervous system (pages 28-36 and 177-179). 

Cell division sequence. Leo Reynolds on Flickr. https://www.flickr.com/photos/lwr/2386410575

A major theme in the book is the depiction of the emergence of the asymmetry that characterises embryological development, a mechanism that is consequential to the emergence of unpaired organs and the differences between the right and left sides of the body. It is nothing short of staggering that this critical phenomenon relies on the simple but fascinating ‘rapid, circular, clockwise motion‘ of hair-like cilia which ‘project from the underside’ of the early foetus. The book portrayed how these structures, oriented ‘at an angle of about 45 degrees‘, generate a ‘biased flow‘ of the fluid which bathes the foetus; in this way, the two sides of the body receive different amounts of signalling proteins, with the result that different genes and structures are activated on opposite sides. The book also described the later mechanisms which maintain asymmetry, for example the local processes that ensure that cells on one side of the body do not cross to the opposite side. An illustrative example of such local signalling processes is how the binding of the protein SLIT to the receptor ROBO hinders neurones from crossing or recrossing the midline; this, the author affirms, is critical to the development of such systems as the visual pathways, and the formation of the connections between the two cerebral hemispheres (page 50-51 and 166 and 172).

By OpenStax – <a rel=”nofollow” class=”external free” href=”https://cnx.org/contents/FPtK1zmh@8.25:fEI3C8Ot@10/Preface”>https://cnx.org/contents/FPtK1zmh@8.25:fEI3C8Ot@10/Preface</a&gt;, CC BY 4.0, Link

The emergence of different internal organs, from the same early embryonic structures, also forms a major part of the book. Typical of foetal development generally, the book demonstrated how each organ evolves entirely by ‘local communication‘ between the cells that will form it. In what is a thoroughly exhaustive account, the author gave several examples of how this strategy leads to the genesis of the endoderm-derived organs such as the lungs, the liver, the pancreas, and the gallbladder, all developing as branches of the gut; a similar mechanism operates in the development of the mesoderm-derived organs such as the spleen, the kidneys, and the urinary tracts. Of all these accounts, the formation of the reproductive systems stood out for the influence it will have on the final body form that will emerge. In exploring this, the author pointed out that the default anatomical gender is female, and the male organs emerge only when the gonads are induced by the protein encoded by the SRY gene on the Y chromosome. The SRY protein, the author added, also commits the embryo to maleness when it switches on other genes such as SOX9, and when it activates molecular mechanisms such as the FGF signalling pathway. Complementing this theme is the depiction of the formation of the sex organs, the female from the Mullerian ducts, and the male from the Wolffian ducts (pages 123-124 and 147-155).

42-17799753. Buggergirl on Flickr. https://www.flickr.com/photos/54220532@N05/5958948468

An equalling compelling theme of the book is the process whereby the ‘body proper‘ is constructed from what is an amorphous and undistinguished early embryonic form. In exploring this captivating feature of embryology, the book describes how elaborate arrays of locally acting genes and signalling particles coordinate the formation of the body. To illustrate this, the book provided such examples as the step-wise evolution of the foetus from the stage of gastrulation – when the embryo is composed of just two discs lying between the amniotic sac and the yolk sac – to the point when the epiblast develops a head and a posterior part; it is important that the latter will contain the primitive streak, the formation of which, the author asserts, is the ‘critical ethical boundary in human development’. Also paramount to the formation of the body form is the differentiation of the epiblast into the endoderm, the mesoderm, and the ectoderm, and the subsequent segmentation of the mesoderm into somites – the precursors of the vertebrae and the muscles. Pivotal to this process of body formation, as with other embryological processes, is the influence of local factors, particularly the genetic interplay of the 13 fundamentally important HOX genes which determine when and where each segment is formed (pages 68-87).

Embryo week 9-10. Lunar Caustic on Flickr. https://www.flickr.com/photos/lunarcaustic/2433149102

Opinion

This book explores the step by step development of the human being, highlighting the simple principles governing what is a rather complex process. Without diluting the clearly academic content, the author still put across the intricate mechanisms at play in such a way as to engender fascination for what is clearly the pre-programmed coordination and execution of human development. Whilst it is inevitable that sections of the book conveyed difficult biological concepts and processes, the details nevertheless occasionally seemed excessive for a book directed at lay readers. Some of the ideas the author discussed were also largely speculative, understandably because embryological development is still in a nascent stage. These apart, the narrative is engaging and focused, and the key messages repeated throughout the book for emphasis. The contents of the book are comprehensive and detailed, providing sufficient academic detail but still conveying to the lay reader the wonder and the intricacy of human development.

Overall assessment

The book covers the subject of embryology quite comprehensively. Whilst the text is rather scholarly, the content is centred on just a few basic principles which the author repeatedly emphasised. The book also highlighted the clinical consequences that arise when the labyrinthine process of foetal development goes wrong, a theme that has ramifications across the breadth of medicine, from genetics to oncology. By highlighting how the various disorders of development emerge, the author succeeds in making embryology singularly relevant to clinically practice. The subject of the book is practical and enlightening, and I recommend it to all doctors.

Book details

Publisher, Place, Year:  Oxford University Press, Oxford, 2014
Number of chapters: 19
Number of pages: 299
ISBN: 978-0-19-967354-4
Star rating: 5
Price: £8.22

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