Nav: Home

Scientists reveal the beautiful simplicity underlying branching patterns in tissue

September 14, 2017

In the centenary year of the publication of a seminal treatise on the physical and mathematical principles underpinning nature - On Growth and Form by D'Arcy Wentworth Thompson - a Cambridge physicist has led a study describing an elegantly simple solution to a puzzle that has taxed biologists for centuries: how complex branching patterns of tissues arise.

Branching patterns occur throughout nature - in trees, ferns and coral, for example - but also at a much finer scale, where they are essential to ensuring that organisms can exchange gases and fluids with the environment efficiently by the maximising the surface area available.

For example, in the small intestine, epithelial tissue is arranged in an array of finger-like protrusions. In other organs, such as kidney, lung, mammary glands, pancreas and prostate, exchange surfaces are packed efficiently around intricate branched epithelial structures.

"On the surface, the question of how these structures grow - structures that may contain as many as 30 or 40 generations of branching - seems incredibly complex," says Professor Ben Simons, who led the study, published today in the journal Cell. Professor Simons holds positions in the University of Cambridge's Cavendish Laboratory and Wellcome Trust/Cancer Research UK Gurdon Institute.

This classic problem of 'branching morphogenesis' has attracted the attention of scientists and mathematicians for centuries. Indeed, the mathematical underpinnings of morphogenesis - the biological process that causes organisms to develop their shape - was the subject of D'Arcy Wentworth Thompson's classic text, published in 1917 by Cambridge University Press. Thompson had been a student at Cambridge, studying zoology at Trinity College, and briefly worked as a Junior Demonstrator in Physiology.

During development, branching structures are orchestrated by stem-like cells that drive a process of ductal growth and division (or 'bifurcation'). Each subsequent branch will then either stop growing, or continue to branch again. In a study published in Nature earlier this year, Professor Simons working in collaboration with Dr Jacco van Rheenen at the Hubrecht Institute in Utrecht showed that, in the mammary gland, these processes of division and termination occur randomly, but with almost equal probability.

"While there's a collective decision-making process going on involving multiple different stem cell types, our discovery that growth occurs almost at the flip of a coin suggested that there may be a very simple rule underpinning it," says Professor Simons.

Professor Simons and his colleague Dr Edouard Hannezo observed that there was very little crossover of the branches - ducts seemed to expand to fill the space, but not overlap. This led them to conjecture that the ducts were growing and dividing, but as soon as a tip touched another branch, it would stop.

"In this way, you generate a perfectly space-filling network, with precisely the observed statistical organisation, via the simplest local instruction: you branch and you stop when you meet a maturing duct," says Dr Hannezo, a Sir Henry Wellcome Postdoctoral Fellow based at the Gurdon Institute. "This has enormous implications for the basic biology. It tells you that complex branched epithelial structures develop as a self-organised process, reliant upon a strikingly simple, but generic, rule, without recourse to a rigid, pre-determined sequence of genetically programmed events."

Although these observations were based on the mammary gland epithelium, by using primary data from Dr Rosemary Sampogna at Columbia University, Professor Anna Philpott in Cambridge and Dr Rakesh Heer at Newcastle University, the researchers were able to show that the same rules governed the embryonic development of the mouse kidney, pancreas and human prostate.

"In the mammary gland, you have a hundred or more fate-restricted stem-like cells participating in this bifurcation-growth-bifurcation process, whereas in the pancreas it's just a handful; but the basic dynamics are the same," says Professor Simons. "The model is aesthetically beautiful, because the rules are so simple and yet they are able to predict the complex branching patterns of these structures."

The researchers say their discovery may offer insights into the development of breast and pancreatic cancer, where the earliest stages of the disease often show an irregular tangled ductal-like organisation.

"A century after the publication of On Growth and Form, it's exciting to see how the concepts of self-organisation and emergence continue to offer fresh perspectives on the development of biological systems, framing new questions about the regulatory mechanisms operating at the cellular and molecular scale," Professor Simons adds.

While it may be too early to tell whether similar rules apply to other branched tissues and organisms, there are interesting parallels: branching in trees appears to follow a similar pattern, for example, with side branches growing and bifurcating until they are shaded or until they are screened by another branch, at which point they stop.

The research was funded by the Wellcome Trust with additional core support from Cancer Research UK and the Medical Research Council.

Dr Sheny Chen from Wellcome's Cellular and Developmental Science team, said: "This is an elegant study that helps us to understand what guides the decisions our cells make during essential developmental processes. It's fascinating to see that such simple rules can govern the generation of such highly complex patterns and that these rules can apply to different branched structures."
-end-
References

Scheele, C et al. Identity and dynamics of mammary stem cells during branching morphogenesis. Nature 542, 313-317 (2017); DOI: 10.1038/nature21046

Hannezo, E et al. A unifying theory of branching morphogenesis. Cell; e-pub 14 Sept 2017; DOI: TBC

University of Cambridge

Related Embryonic Development Articles:

New tools to study the origin of embryonic stem cells
Researchers at Karolinska Institutet have identified cell surface markers specific for the very earliest stem cells in the human embryo.
Dad's exposure to phthalates in plastics may affect embryonic development
A new study led by environmental health scientist Richard Pilsner at the University of Massachusetts Amherst, one of the first to investigate whether preconception exposures to phthalates in fathers has an effect on reproductive success via embryo quality, found that exposures from select chemicals tested were associated with 'a pronounced decrease in blastocyst quality' at an early stage in embryo development.
Vitamin D increases the number of blood stem cells during embryonic development
Short exposure to vitamin D influences the number of blood stem cells in human umbilical cords and zebrafish embryos, Harvard researchers report in Cell Reports.
Jaw-dropping research explains mouth formation during embryonic development
Whitehead Institute researchers have identified an area in the developing face of embryonic frogs that unzips to form the mouth.
The first AI system for human embryonic state analysis is available for testing
The first implementation of Embryonic.AI was launched by LifeMap Discovery, Inc, a subsidiary of BioTime, Inc and is freely available for beta testing.
Asynchronous cell cycle phase key to critical stage of animal embryonic development
A pair of University of Tsukuba researchers discovered that the synchronous mitosis of early embryonic development switches to a patterned form at the 11th cell division following removal of a cell cycle compensatory mechanism.
Drug makes stem cells become 'embryonic' again
If you want to harness the full power of stem cells, all you might need is an eraser -- in the form of a drug that can erase the tiny labels that tell cells where to start reading their DNA.
Oncogene controls stem cells in early embryonic development
Many animal species delay the development of their embryos to ensure that their offspring is born at a favorable time.
'BPA-free' plastic accelerates embryonic development, disrupts reproductive system
Companies advertise 'BPA-free' as a safer version of plastic products ranging from water bottles to sippy cups to toys.
New study of gene mutations causing Leigh syndrome shows effects on embryonic development
Embryonic stem cells (ESCs) prove to be an excellent model system for determining at what stage the mutations in the Complex I gene, known to cause Leigh syndrome, begin to affect embryonic development.

Related Embryonic Development Reading:

The Embryonic Development of Drosophila melanogaster
by Jose A. Campos-Ortega (Author), Volker Hartenstein (Author)

" . . . but our knowledge is so weak that no philosopher will ever be able to completely explore the nature of even a fly . . . " * Thomas Aquinas "In Symbolum Apostolorum" 079 RSV p/96 This is a monograph on embryogenesis of the fruit fly Drosophila melanogaster, conceived as a reference book on the morphology of embryonic development. A monograph of this extent and content is not yet available in the literature on Drosophila embryology, and we believe that there is a real need for it. Thanks to the pro­ gress achieved during the last ten years in the fields of develop­ mental and... View Details


Introduction to Embryonic Development
by S. Oppenheimer (Author)

Ideal for those with little or no background in genetics and cellular or developmental biology, this exploration of embryology and the molecular aspects of development explains each concept from first principles. View Details


Introduction to Embryonic Development (3rd Edition)
by S. Oppenheimer (Author), G. Lefevre (Author)

Ideal for those with little or no background in genetics and cellular or developmental biology, this exploration of embryology and the molecular aspects of development explains each concept from first principles. View Details


Langman's Medical Embryology
by T.W. Sadler PhD (Author)

Publisher’s Note:   Products purchased from 3rd Party sellers are not guaranteed by the Publisher for quality, authenticity, or access to any online entitlements included with the product.
Offering exceptional full color diagrams and clinical images, Langman's Medical Embryology, 13e helps medical, nursing, and health professions students develop a basic understanding of embryology and its clinical relevance. Concise chapter summaries, captivating clinical correlates boxes, clinical problems, and a clear, concise writing style make the subject... View Details


Egg Incubation: Its Effects on Embryonic Development in Birds and Reptiles
by D. Charles Deeming (Editor), Mark W. J. Ferguson (Editor)

A recent rapid expansion in our knowledge of embryonic development in birds and reptiles has created a need for a book that comprehensively reviews and synthesizes data relating to incubation effects on the embryonic development of these two vertebrate classes. The contributors to this book aptly deal with these issues in logical parts. The first deals with the structure, shape, and function of eggs. The second examines the effects of the four main parameters, e.g. temperature, water relations, respiratory gas exchange, and turning, on the process of incubation. The third section deals with... View Details


Glial Cells: Embryonic Development, Types/Functions and Role in Disease (Neuroscience Research Progress: Cells Biology Research Progress)
by Charanjit Kaur (Author), Charanjit Kaur (Editor), Eng-Ang Ling (Editor)

View Details


The Embryonic Development of the Ovary and Testis of the Mammals: A Dissertation Submitted to the Faculties of the Graduate Schools of Arts, ... Doctor of Philosophy, Department of Zoology
by Bennet Mills Allen (Author)

Excerpt from The Embryonic Development of the Ovary and Testis of the Mammals: A Dissertation Submitted to the Faculties of the Graduate Schools of Arts, Literature and Science, in Candidacy for the Degree of Doctor of Philosophy, Department of Zoology

Three distinct regions may be distinguished in this genital ridge, each of which occupies, roughly speaking, one-third of its length. N amed in their order, they are: (1) the rete; (2) the sex gland; (3) the mesenteric ridge.

About the Publisher

Forgotten Books publishes hundreds of thousands of rare and classic books. Find more at... View Details


Embryonic and Postembryonic Development of the House Fly (Musca domestica L.)
by George E. Cantwell (Author)

Washington 1976. 8vo., 69pp., photo illustrations, original printed wraps. Depository library stamp on title page and front. Ink number on front. VG. View Details


The Development and the Embryonic Anatomy of the Human Gastro-Intestinal Tract: a New Basis for the Study of Anomalies of the Gastro-Intestinal Tract
by Niels Lauge-Hansen (Author)

View Details


Embryonic Development of Bhakur, Catla Catla: A study of morpho-embryological and histo-embryological development of catla catla
by Jawan Tumbahangfe (Author), Bharat Raj Subba (Author)

Sample of fertilized eggs were collected from the incubation tank using dropper in a petridish along with water and developing stages were observed under microscope and photographed was taken every 10minutes interval. For histological study embryos were fixed in freshly prepared Bouin’s fluid at room temperature 10-12hrs and washed with running tap water for 8-10 hrs. Chorions were manually removed and the naked embryos were embedded in paraffin and sectioned at 7µm with microtome machine. Sections were double stain with hematoxylen and eosin and mounted in DPX and observed and... View Details

Best Science Podcasts 2018

We have hand picked the best science podcasts for 2018. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

The Person You Become
Over the course of our lives, we shed parts of our old selves, embrace new ones, and redefine who we are. This hour, TED speakers explore ideas about the experiences that shape the person we become. Guests include aerobatics pilot and public speaker Janine Shepherd, writers Roxane Gay and Taiye Selasi, activist Jackson Bird, and fashion executive Kaustav Dey.
Now Playing: Science for the People

#478 She Has Her Mother's Laugh
What does heredity really mean? Carl Zimmer would argue it's more than your genes along. In "She Has Her Mother’s Laugh: The Power, Perversions, and Potential of Heredity", Zimmer covers the history of genetics and what kinship and heredity really mean when we're discovering how to alter our own DNA, and, potentially, the DNA of our children.