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"Views of a Fetus in the Womb", Leonardo da Vinci, ca. 1510-1512. The subject of prenatal development is a major subset of developmental biology.

Developmental biology is the study of the process by which organisms grow and develop. Modern developmental biology studies the genetic control of cell growth, differentiation and "morphogenesis", which is the process that gives rise to tissues, organs and anatomy.

Perspectives[link]

The development of a new life is a spectacular process and represents a masterpiece of temporal and spatial control of gene expression. Developmental genetics studies the effect that genes have in a phenotype, given normal or abnormal epigenetic parameters. The findings of developmental biology can help to understand developmental abnormalities such as chromosomal aberrations that cause Down syndrome. An understanding of the specialization of cells during embryogenesis has provided information on how stem cells specialize into specific tissues and organs. This information has led, for example, to the cloning of specific organs for medical purposes.^[1][2] Another biologically important process that occurs during development is apoptosis—programmed cell death or "suicide." Many developmental models are used to elucidate the physiology and molecular basis of this cellular process. Similarly, a deeper understanding of developmental biology can foster greater progress in the treatment of congenital disorders and diseases, e.g. studying human sex determination can lead to treatment for disorders such as congenital adrenal hyperplasia.

Developmental model organisms[link]

Gene expression pattern determined by histochemical GUS assays in Physcomitrella patens. The Polycomb gene FIE is expressed (blue) in unfertilised egg cells of the moss Physcomitrella patens (right) and expression ceases after fertilisation in the developing diploid sporophyte (left). In situ GUS staining of two female sex organs (archegonia) of a transgenic plant expressing a translational fusion of FIE-uidA under control of the native FIE promoter^[3]

Often used model organisms in developmental biology include the following:

• Vertebrates
  • Zebrafish Danio rerio^[4]
  • Medakafish Oryzias latipes
  • Fugu (pufferfish) Takifugu rubripes
  • Frog Xenopus laevis, Xenopus tropicalis^[5]
  • Chicken Gallus gallus
  • Mouse Mus musculus (Mammalian embryogenesis)^[6]

• Invertebrates
  • Lancelet Branchiostoma lanceolatum
  • Ascidian Ciona intestinalis
  • Sea urchin Strongylocentrotus purpuratus
  • Roundworm Caenorhabditis elegans
  • Fruit fly Drosophila melanogaster (Drosophila embryogenesis)

• Plants (Plant embryogenesis)
  • Physcomitrella patens ^[3]
  • Arabidopsis thaliana
  • Maize
  • Snapdragon Antirrhinum majus

• Other
  • Slime mold Dictyostelium discoideum

Studied phenomena[link]

Cell differentiation[link]

Differentiation is the formation of cell types, from what is originally one cell – the zygote or spore. The formation of cell types like nerve cells occurs with a number of intermediary, less differentiated cell types. A cell stays a certain cell type by maintaining a particular pattern of gene expression.^[7] This depends on regulatory genes, e.g. for transcription factors and signaling proteins. These can take part in self-perpetuating circuits in the gene regulatory network, circuits that can involve several cells that communicate with each other.^[8] External signals can alter gene expression by activating a receptor, which triggers a signaling cascade that affects transcription factors. For example, the withdrawal of growth factors from myoblasts causes them to stop dividing and instead differentiate into muscle cells.^[9]

Embryonic development[link]

The initial stages of human embryogenesis.

Embryogenesis is the step in the life cycle after fertilisation – the development of the embryo, starting from the zygote (fertilised egg). Organisms can differ drastically in how the embryo develops, especially when they belong to different phyla. For example, embryonal development in placental mammals starts with cleavage of the zygote into eight uncommited cells, which then form a ball (morula). The outer cells become the trophectoderm or trophoblast, which will form in combination with maternal uterine endometrial tissue the placenta, needed for fetal nurturing via maternal blood, while inner cells become the inner cell mass that will form all fetal organs (the bridge between these two parts eventually forms the umbilical cord). In contrast, the fruit fly zygote first forms a sausage-shaped syncytium, which is still one cell but with many cell nuclei.^[10]

Patterning is important for determining which cells develop into which organs. This is mediated by signaling between adjacent cells by proteins on their surfaces, and by gradients of signaling secreted molecules.^[11] An example is retinoic acid, which forms a gradient in the head to tail direction in animals. Retinoic acid enters cells and activates Hox genes in a concentration-dependent manner – Hox genes differ in how much retinoic acid they require for activation and will thus show differential rostral expression boundaries, in a colinear fashion with their genomic order. As Hox genes code for transcription factors, this causes different activated combinations of both Hox and other genes in discrete anteroposterior transverse segments of the neural tube (neuromeres) and related patterns in surrounding tissues, such as branchial arches, lateral mesoderm, neural crest, skin and endoderm, in the head to tail direction.^[12] This is important for e.g. the segmentation of the spine in vertebrates.^[11]

Embryonic development does not always proceed correctly, and errors can result in birth defects or miscarriage. Often the reason is genetic (mutation or chromosome abnormality), but there can be environmental influence (like teratogens) or stochastic events.^[13][14] Abnormal development caused by mutation is also of evolutionary interest as it provides a mechanism for changes in body plan (see evolutionary developmental biology).^[15]

Growth[link]

Growth is the enlargement of a tissue or organism. Growth continues after the embryonal stage, and occurs through cell proliferation, enlargement of cells or accumulation of extracellular material. In plants, growth results in an adult organism that is strikingly different from the embryo. The proliferating cells tend to be distinct from differentiated cells (see stem cell and progenitor cell). In some tissues proliferating cells are restricted to specialised areas, such as the growth plates of bones.^[16] But some stem cells migrate to where they are needed, such as mesenchymal stem cells which can migrate from the bone marrow to form e.g. muscle, bone or adipose tissue.^[17] The size of an organ frequently determines its growth, as in the case of the liver which grows back to its previous size if a part is removed. Growth factors, such as fibroblast growth factors in the animal embryo and growth hormone in juvenile mammals, also control the extent of growth.^[16]

Metamorphosis[link]

Most animals have a larval stage, with a body plan different from that of the adult organism. The larva abrubtly develops into an adult in a process called metamorphosis. For example, caterpillars (butterfly larvae) are specialized for feeding whereas adult butterflies (imagos) are specialised for flight and reproduction. When the caterpillar has grown enough, it turns into an immobile pupa. Here, the imago develops from imaginal discs found inside the larva.^[18]

Regeneration[link]

Regeneration is the reactivation of development so that a missing body part grows back. This phenomenon has been studied particularly in salamanders, where the adults can reconstruct a whole limb after it has been amputated.^[19] Researchers hope to one day be able to induce regeneration in humans (see regenerative medicine).^[20] There is little spontaneous regeneration in adult humans, although the liver is a notable exception. Like for salamanders, the regeneration of the liver involves dedifferentiation of some cells to a more embryonal state.^[19]

Developmental systems biology[link]

Computer simulation of multicellular development is a research methodology to understand the function of the very complex processes involved in the development of organisms. This includes simulation of cell signaling, multicell interactions and regulatory genomic networks in development of multicellular structures and processes (see French flag model or Biological Physics of the Developing Embryo for literature). Minimal genomes for minimal multicellular organisms may pave the way to understand such complex processes in vivo.

See also[link]

References[link]

External links[link]

Wikibooks has more on the topic of Developmental biology

• Developmental Biology of Plants and Animals
• Developmental Biology - 8th Edition by Scott Gilbert (online textbook)

Marc W. Kirschner
Born	(1945-02-28)February 28, 1945 Chicago, Illinois
Residence	Massachusetts
Nationality	United States
Fields	Cell (biology), Systems biology
Institutions	Harvard Medical School University of California, San Francisco Princeton University
Alma mater	University of California, Berkeley (PhD) Northwestern University (BA)
Doctoral advisor	Howard Schachman
Known for	cell cycle, embryonic development, facilitated evolution

Marc W. Kirschner (born February 28, 1945) is an American cell biologist and biochemist and the founding chair of the Department of Systems Biology at Harvard Medical School. His research involves problems in cell and developmental biology, such as the dynamics and function of the cytoskeleton, the regulation of the cell cycle, and the process of signaling in embryos, as well as the evolution of the vertebrate body plan, and applying mathematical approaches to biology.

Biography[link]

Kirschner was born in Chicago, Illinois, on February 28, 1945. He graduated from Northwestern University with a B.A. in chemistry in 1966. In 1971, he received his doctorate in biochemistry from the University of California, Berkeley. He held post-doctoral positions at UC Berkeley and at the University of Oxford in England. He became assistant professor at Princeton University in 1972. In 1978 he was made professor at the University of California, San Francisco. In 1993, he moved to Harvard Medical School, where he served as the chair of the new Department of Cell Biology for a decade. He became the founding chair of the HMS Department of Systems Biology in 2003. He was named the John Franklin Enders University Professor in 2009.^[1]

Scientific Contributions[link]

Kirschner studies how cells divide, how they generate their shape, how they control their size, and how embryos develop. In his eclectic lab, developmental work on the frog coexists with biochemical work on mechanism of ubiquitination, cytoskeleton assembly or signal transduction.

At Princeton, his early work on microtubules established their unusual molecular assembly from tubulin proteins and identified the first microtubule-stabilizing protein tau,^[2] later shown to be a major component of the neurofibrillary tangles in Alzheimer's disease. In studies at UC San Francisco of the frog embryo as a model system of cell development, Kirschner identified the first inducer of embryonic differentiation, fibroblast growth factor (FGF),^[3] an early finding in the field of signal transduction.

Kirschner's lab is also known for uncovering the basic mechanisms of the cell cycle in eukaryotic cells. Working in Xenopus (frog) egg extracts, Kirschner and Andrew Murray showed that cyclin synthesis drives the cell cycle ^[4] and, later, that ubiquitin regulates levels of cyclin by marking the cell-cycle molecule for destruction ^[5]. His lab discovered and purified many of the components involved in cell cycle progression, including anaphase promoting complex (APC), the complex that ubiquitinates cyclin B.

A second noted^[6] finding was his discovery, with Tim Mitchison, of the dynamic instability of microtubules,^[7] a fundamental property that allows microtubules to explore the space within a cell efficiently.^[8] In mitosis, for example, microtubules form the spindle that separates the chromosomes. The first step in spindle formation is the nucleation of microtubules by microtubule-organizing centers, which then grow in all directions. Microtubules that attach to a chromosome are stabilized and are therefore retained to form part of the spindle. Because of dynamic instability, some individual microtubules that are not stabilized are at risk of collapse (or “catastrophe” as Kirschner named it), allowing re-use of the tubulin monomers. This recognition of self-organization in biological systems has been highly influential, and helped shape the view of the cytoplasm as a collection of dynamic molecular machines.^[9]

In addition to these contributions, Kirschner has interests in the evolutionary origins of the vertebrate body plan, and in particular the origins of the chordate nervous system. He has been involved in using mathematical approaches to learn about central biological questions. For example, a model of the Wnt pathway he developed in collaboration with the late Reinhart Heinrich showed that new properties and constraints emerge when the individual biochemical steps are combined into a complete pathway.^[10]

In two books co-authored with John Gerhart, Kirschner has described the cellular and developmental underpinnings of the evolution of organisms. In the most recent book, Kirschner and Gerhart proposed a new theory of "facilitated variation" that aims to answer the question: How can small, random genetic changes be converted into useful changes in complex body parts? ^[11]

Public Service[link]

Kirschner has been an advocate for federal biomedical research funding and served as first chair of the Joint Steering Committee for Public Policy, a coalition of scientific societies he helped create in 1993 to educate the U.S. Congress on biomedical research and lobby for public funding of it.^[12]

Kirschner helped launch the monthly, peer-reviewed journal PLoS Biology in October 2003 as a member of the editorial board and senior author of a paper in the inaugural issue. The journal was the first publishing venture from the San Francisco-based Public Library of Science (PLoS), which had begun three years ago as a grassroots organization of scientists advocating free and unrestricted access to the scientific literature^[13]

Books[link]

• with John Gerhart, Cells, Embryos, and Evolution: Toward a Cellular and Developmental Understanding of Phenotypic Variation and Evolutionary Adaptability (Blackwell's, 1997) ISBN 0-86542-574-4
• with John Gerhart, The Plausibility of Life: Resolving Darwin's Dilemma ([1]Yale University Press 2005) ISBN 0-300-10865-6

Awards and associations[link]

• 1989-present - Member, National Academy of Sciences
• 1989-present - Member, American Academy of Arts and Sciences^[14]
• 1990-1991 - President, American Society for Cell Biology
• 1996 - Public Service Award, American Society for Cell Biology
• 1999-present - Foreign Member, Royal Society of London
• 1999-present - Foreign Member, Academia Europaea
• 2001 - William C. Rose Award, American Society for Biochemistry and Molecular Biology
• 2001 - Gairdner Foundation International Award (Canada)^[15]
• 2003 - Rabbi Shai Shacknai Memorial Prize in Immunology and Cancer Research, Hebrew University-Hadassah Medical School, Jerusalem
• 2003 E.B. Wilson Medal, American Society for Cell Biology (the ASCB's highest honor)
• 2004 - Dickson Prize for Science, Carnegie Mellon University^[16]

References[link]

External links[link]

• Marc W. Kirschner, Ph.D., (Faculty page), Harvard Department of Systems Biology.
• Marc Kirschner scientific publications list on Pubget.
• Essay: "Cell Biology as a World View" by Mark Kirschner, Molecular Biology of the Cell, 15 November 2010 doi:10.1091/mbc.E10-04-0343.
• Video: Marc W. Kirschner iBioSeminars talk: "The Origin of Vertebrates, a 3-part lecture on evolution and developmental biology, taped by iBioSeminars January 2008. (Also available at YouTube and on iTunesU).
• Video: "Systems questions in cell biology", NIH Director's Wednesday Afternoon Lecture Series, 17 October 2007. (Audio podcast also available.)
• Video: Lecture on evolution in Cambridge, Mass., 30 November 2005 taped by WGBH Forum Network. (Includes explanation of "facilitated variation.")
• Marc Kirschner and John Gerhart: An email interview by Gregg Ross on American Scientist Online, November 2005.
• Audio: Marc Kirschner interview in "Resolving Darwin's dilemma," On Point radio show at WBUR Boston, 18 October 2005.
• Plausibility of Life discussed in "Evolving Evolution," by Israel Rosenfield and Edward Ziff, New York Review of Books, 11 May 2006