Cell fate determination

Last updated

Within the field of developmental biology, one goal is to understand how a particular cell develops into a final cell type, known as fate determination. Within an embryo, several processes play out at the cellular and tissue level to create an organism. These processes include cell proliferation, differentiation, cellular movement [1] and programmed cell death. [2] [3] Each cell in an embryo receives molecular signals from neighboring cells in the form of proteins, RNAs and even surface interactions. Almost all animals undergo a similar sequence of events during very early development, a conserved process known as embryogenesis. [4] During embryogenesis, cells exist in three germ layers, and undergo gastrulation. While embryogenesis has been studied for more than a century, it was only recently (the past 25 years or so) that scientists discovered that a basic set of the same proteins and mRNAs are involved in embryogenesis. Evolutionary conservation is one of the reasons that model systems such as the fly (Drosophila melanogaster), the mouse (Mus musculus), and other organisms are used as models to study embryogenesis and developmental biology. Studying model organisms provides information relevant to other animals, including humans. While studying the different model systems, cells fate was discovered to be determined via multiple ways, two of which are by the combination of transcription factors the cells have and by the cell-cell interaction. [5] Cells' fate determination mechanisms were categorized into three different types, autonomously specified cells, conditionally specified cells, or syncytial specified cells. Furthermore, the cells' fate was determined mainly using two types of experiments, cell ablation and transplantation. [6] The results obtained from these experiments, helped in identifying the fate of the examined cells.

Contents

Cell fate

The development of new molecular tools including GFP, and major advances in imaging technology including fluorescence microscopy, have made possible the mapping of the cell lineage of Caenorhabditis elegans including its embryo. [7] [8] This technique of fate mapping is used to study cells as they differentiate and gain specified function. Merely observing a cell as it becomes differentiated during embryogenesis provides no indication of the mechanisms that drive the specification. The use of molecular techniques, including gene and protein knock downs, knock outs and overexpression allows investigation into the mechanisms of fate determination. [9] [10] [11] [12] [13] Improvements in imaging tools including live confocal microscopy and super resolution microscopy [14] allow visualization of molecular changes in experimentally manipulated cells as compared to controls. Transplantation experiments can also be used in conjunction with the genetic manipulation and lineage tracing. Newer cell fate determination techniques include lineage tracing performed using inducible Cre-lox transgenic mice, where specific cell populations can be experimentally mapped using reporters like brainbow, a colorful reporter that is useful in the brain and other tissues to follow the differentiation path of a cell. [15]

During embryogenesis, for a number of cell cleavages (the specific number depends on the type of organism) all the cells of an embryo will be morphologically and developmentally equivalent. This means, each cell has the same development potential and all cells are essentially interchangeable, thus establishing an equivalence group. The developmental equivalence of these cells is usually established via transplantation and cell ablation experiments. As embryos mature, more complex fate determination occurs as structures appear, and cells differentiate, beginning to perform specific functions. Under normal conditions, once cells have a specified fate and have undergone cellular differentiation, they generally cannot return to less specified states; however, new research indicates that de-differentiation is possible under certain conditions including wound healing and cancer. [16] [17]

The determination of a cell to a particular fate can be broken down into two states where the cell can be specified (committed) or determined. In the state of being committed or specified, the cell type is not yet determined and any bias the cell has toward a certain fate can be reversed or transformed to another fate. If a cell is in a determined state, the cell's fate cannot be reversed or transformed. In general, this means that a cell determined to differentiate into a brain cell cannot be transformed into a skin cell. Determination is followed by differentiation, the actual changes in biochemistry, structure, and function that result in specific cell types. Differentiation often involves a change in appearance as well as function. [18]

Modes of specification

There are three general ways a cell can become specified for a particular fate; they are autonomous specification, conditional specification and syncytial specification. [19]

Autonomous specification

This type of specification results from cell-intrinsic properties; it gives rise to mosaic development. The cell-intrinsic properties arise from a cleavage of a cell with asymmetrically expressed maternal cytoplasmic determinants (proteins, small regulatory RNAs and mRNA). Thus, the fate of the cell depends on factors secreted into its cytoplasm during cleavage. Autonomous specification was demonstrated in 1887 by a French medical student, Laurent Chabry, working on tunicate embryos. [20] [21] This asymmetric cell division usually occurs early in embryogenesis.

Positive feedback can create asymmetry from homogeneity. In cases where the external or stimuli that would cause asymmetry are very weak or disorganized, through positive feedback the system can spontaneously pattern itself. Once the feedback has begun, any small initial signaling is magnified and thus produces an effective patterning mechanism. [22] This is normally what occurs in the case of lateral inhibition in which neighboring cells induce specification via inhibitory or inducing signals (see Notch signaling). This kind of positive feedback at the single cell level and tissue level is responsible for symmetry breaking, which is an all-or-none process whereas once the symmetry is broken, the cells involved become very different. Symmetry breaking leads to a bistable or multistable system where the cell or cells involved are determined for different cell fates. The determined cells continue on their particular fate even after the initial stimulatory/inhibitory signal is gone, giving the cells a memory of the signal. [22]

The specific results of cell ablation and isolation that highlights autonomously specified cells are the following. If ablation of a tissue from a certain cell occurred, the cell will have a missing part. As a result, the removed tissue was autonomously specified since the cell was not able to make up for the missing part [19] [20] [23] .  Furthermore, if specific cells were isolated in a petri dish from the whole structure, these cells will still form the structure or tissue they were going to form initially. [19] [20] [23] In other words, the signaling to form a specific tissue is within the tissue not coming from a central organ or system.

Conditional specification

In contrast to the autonomous specification, this type of specification is a cell-extrinsic process that relies on cues and interactions between cells or from concentration-gradients of morphogens. Inductive interactions between neighboring cells is the most common mode of tissue patterning. In this mechanism, one or two cells from a group of cells with the same developmental potential are exposed to a signal (morphogen) from outside the group. Only the cells exposed to the signal are induced to follow a different developmental pathway, leaving the rest of the equivalence group unchanged. Another mechanism that determines the cell fate is regional determination (see Regional specification). As implied by the name, this specification occurs based on where within the embryo the cell is positioned, it is also known as positional value. [24] This was first observed when mesoderm was taken from the prospective thigh region of a chick embryo, was grafted onto the wing region and did not transform to wing tissue, but instead into toe tissue. [25]

In conditionally specified cells, the designated cell requires signaling from an exterior cell. Therefore, if the tissue was ablated, the cell will be able to regenerate or signal to reform the initially ablated tissue. [19] [20] [23] In addition, if a belly tissue for example was removed and transplanted in the back, the new forming tissue will be a back tissue. [19] [20] [23] This result is seen because the surrounding cells and tissues influence the newly forming cell.

Syncytial specification

This type of a specification is a hybrid of the autonomous and conditional that occurs in insects. This method involves the action of morphogen gradients within the syncytium. As there are no cell boundaries in the syncytium, these morphogens can influence nuclei in a concentration-dependent manner. It was discovered that cellularization of the blastoderm took place either during or before the specifications of body regions. [26] Also, one cell could contain more than one nucleus due to fusion of multiple uninuclear cells. As a result, the variable cleavage of the cells will make the cells hard to be committed or determined to one cell fate. [23] At the end of cellularization, the autonomously specified cells become distinguished from the conditionally specified once.

See also

Plant embryogenesis, see Lau S et al., Cell-cell communication in Arabidopsis early embryogenesis. Eur J Cell Biol 2010, 89:225-230. [27]

For a good review of the part of the history of morphogen signaling and development see Briscoe J, Making a grade: Sonic Hedgehog signalling and the control of neural cell fate. [28]

In systems biology, cell-fate determination is predicted to exhibit certain dynamics, such as attractor-convergence (the attractor can be an equilibrium point, limit cycle or strange attractor) or oscillatory. [29]

Related Research Articles

Developmental biology is the study of the process by which animals and plants grow and develop. Developmental biology also encompasses the biology of regeneration, asexual reproduction, metamorphosis, and the growth and differentiation of stem cells in the adult organism.

Morphogenesis is the biological process that causes a cell, tissue or organism to develop its shape. It is one of three fundamental aspects of developmental biology along with the control of tissue growth and patterning of cellular differentiation.

<span class="mw-page-title-main">Cellular differentiation</span> Developmental biology

Cellular differentiation is the process in which a stem cell changes from one type to a differentiated one. Usually, the cell changes to a more specialized type. Differentiation happens multiple times during the development of a multicellular organism as it changes from a simple zygote to a complex system of tissues and cell types. Differentiation continues in adulthood as adult stem cells divide and create fully differentiated daughter cells during tissue repair and during normal cell turnover. Some differentiation occurs in response to antigen exposure. Differentiation dramatically changes a cell's size, shape, membrane potential, metabolic activity, and responsiveness to signals. These changes are largely due to highly controlled modifications in gene expression and are the study of epigenetics. With a few exceptions, cellular differentiation almost never involves a change in the DNA sequence itself. However, metabolic composition does get altered quite dramatically where stem cells are characterized by abundant metabolites with highly unsaturated structures whose levels decrease upon differentiation. Thus, different cells can have very different physical characteristics despite having the same genome.

<span class="mw-page-title-main">Neural tube</span> Developmental precursor to the central nervous system

In the developing chordate, the neural tube is the embryonic precursor to the central nervous system, which is made up of the brain and spinal cord. The neural groove gradually deepens as the neural fold become elevated, and ultimately the folds meet and coalesce in the middle line and convert the groove into the closed neural tube. In humans, neural tube closure usually occurs by the fourth week of pregnancy.

<span class="mw-page-title-main">Blastulation</span> Sphere of cells formed during early embryonic development in animals

Blastulation is the stage in early animal embryonic development that produces the blastula. In mammalian development the blastula develops into the blastocyst with a differentiated inner cell mass and an outer trophectoderm. The blastula is a hollow sphere of cells known as blastomeres surrounding an inner fluid-filled cavity called the blastocoel. Embryonic development begins with a sperm fertilizing an egg cell to become a zygote, which undergoes many cleavages to develop into a ball of cells called a morula. Only when the blastocoel is formed does the early embryo become a blastula. The blastula precedes the formation of the gastrula in which the germ layers of the embryo form.

<span class="mw-page-title-main">Gastrulation</span> Stage in embryonic development in which germ layers form

Gastrulation is the stage in the early embryonic development of most animals, during which the blastula, or in mammals the blastocyst is reorganized into a two-layered or three-layered embryo known as the gastrula. Before gastrulation, the embryo is a continuous epithelial sheet of cells; by the end of gastrulation, the embryo has begun differentiation to establish distinct cell lineages, set up the basic axes of the body, and internalized one or more cell types including the prospective gut.

<span class="mw-page-title-main">Blastocyst</span> Structure formed around day 5 of mammalian embryonic development

The blastocyst is a structure formed in the early embryonic development of mammals. It possesses an inner cell mass (ICM) also known as the embryoblast which subsequently forms the embryo, and an outer layer of trophoblast cells called the trophectoderm. This layer surrounds the inner cell mass and a fluid-filled cavity known as the blastocoel. In the late blastocyst the trophectoderm is known as the trophoblast. The trophoblast gives rise to the chorion and amnion, the two fetal membranes that surround the embryo. The placenta derives from the embryonic chorion and the underlying uterine tissue of the mother.

<i>Drosophila</i> embryogenesis Embryogenesis of the fruit fly Drosophila, a popular model system

Drosophila embryogenesis, the process by which Drosophila embryos form, is a favorite model system for genetics and developmental biology. The study of its embryogenesis unlocked the century-long puzzle of how development was controlled, creating the field of evolutionary developmental biology. The small size, short generation time, and large brood size make it ideal for genetic studies. Transparent embryos facilitate developmental studies. Drosophila melanogaster was introduced into the field of genetic experiments by Thomas Hunt Morgan in 1909.

Organogenesis is the phase of embryonic development that starts at the end of gastrulation and continues until birth. During organogenesis, the three germ layers formed from gastrulation form the internal organs of the organism.

<span class="mw-page-title-main">Embryoid body</span> Three-dimensional aggregate of pluripotent stem cells

Embryoid bodies (EBs) are three-dimensional aggregates of pluripotent stem cells.

<span class="mw-page-title-main">Morphogen</span> Biological substance that guides development by non-uniform distribution

A morphogen is a substance whose non-uniform distribution governs the pattern of tissue development in the process of morphogenesis or pattern formation, one of the core processes of developmental biology, establishing positions of the various specialized cell types within a tissue. More specifically, a morphogen is a signaling molecule that acts directly on cells to produce specific cellular responses depending on its local concentration.

<span class="mw-page-title-main">Neural crest</span> Pluripotent embyronic cell group giving rise to diverse cell lineages

Neural crest cells are a temporary group of cells that arise from the embryonic ectoderm germ layer, and in turn give rise to a diverse cell lineage—including melanocytes, craniofacial cartilage and bone, smooth muscle, peripheral and enteric neurons and glia.

Gametogonium are stem cells for gametes located within the gonads. They originate from primordial germ cells, which have migrated to the gonads. Male gametogonia which are located within the testes during development and adulthood are called spermatogonium. Female gametogonia, known as oogonium, are found within the ovaries of the developing foetus and were thought to be depleted at or after birth. Spermatogonia and oogonia are classified as sexually differentiated germ cells.

Decapentaplegic (Dpp) is a key morphogen involved in the development of the fruit fly Drosophila melanogaster and is the first validated secreted morphogen. It is known to be necessary for the correct patterning and development of the early Drosophila embryo and the fifteen imaginal discs, which are tissues that will become limbs and other organs and structures in the adult fly. It has also been suggested that Dpp plays a role in regulating the growth and size of tissues. Flies with mutations in decapentaplegic fail to form these structures correctly, hence the name. Dpp is the Drosophila homolog of the vertebrate bone morphogenetic proteins (BMPs), which are members of the TGF-β superfamily, a class of proteins that are often associated with their own specific signaling pathway. Studies of Dpp in Drosophila have led to greater understanding of the function and importance of their homologs in vertebrates like humans.

In developmental biology, the cells that give rise to the gametes are often set aside during embryonic cleavage. During development, these cells will differentiate into primordial germ cells, migrate to the location of the gonad, and form the germline of the animal.

In the field of developmental biology, regional differentiation is the process by which different areas are identified in the development of the early embryo. The process by which the cells become specified differs between organisms.

<span class="mw-page-title-main">French flag model</span> Biological model

The French flag model is a conceptual definition of a morphogen, described by Lewis Wolpert in the 1960s. A morphogen is defined as a signaling molecule that acts directly on cells to produce specific cellular responses dependent on morphogen concentration. During early development, morphogen gradients generate different cell types in distinct spatial order. French flag patterning is often found in combination with others: vertebrate limb development is one of the many phenotypes exhibiting French flag patterning overlapped with a complementary pattern.

Proneural genes encode transcription factors of the basic helix-loop-helix (bHLH) class which are responsible for the development of neuroectodermal progenitor cells. Proneural genes have multiple functions in neural development. They integrate positional information and contribute to the specification of progenitor-cell identity. From the same ectodermal cell types, neural or epidermal cells can develop based on interactions between proneural and neurogenic genes. Neurogenic genes are so called because loss of function mutants show an increase number of developed neural precursors. On the other hand, proneural genes mutants fail to develop neural precursor cells.

<i>Homeotic protein bicoid</i> Protein-coding gene in the species Drosophila melanogaster

Homeotic protein bicoid is encoded by the bcd maternal effect gene in Drosophilia. Homeotic protein bicoid concentration gradient patterns the anterior-posterior (A-P) axis during Drosophila embryogenesis. Bicoid was the first protein demonstrated to act as a morphogen. Although bicoid is important for the development of Drosophila and other higher dipterans, it is absent from most other insects, where its role is accomplished by other genes.

The Spemann-Mangold organizer is a group of cells that are responsible for the induction of the neural tissues during development in amphibian embryos. First described in 1924 by Hans Spemann and Hilde Mangold, the introduction of the organizer provided evidence that the fate of cells can be influenced by factors from other cell populations. This discovery significantly impacted the world of developmental biology and fundamentally changed the understanding of early development.

References

  1. ↑ Wallingford, John B; Fraser, Scott E; Harland, Richard M (2002-06-01). "Convergent Extension: The Molecular Control of Polarized Cell Movement during Embryonic Development". Developmental Cell. 2 (6): 695–706. doi: 10.1016/S1534-5807(02)00197-1 . ISSN   1534-5807. PMID   12062082.
  2. ↑ Miura, Masayuki; Yamaguchi, Yoshifumi (2015-02-23). "Programmed Cell Death in Neurodevelopment". Developmental Cell. 32 (4): 478–490. doi: 10.1016/j.devcel.2015.01.019 . ISSN   1534-5807. PMID   25710534.
  3. ↑ Ranganath, R. M.; Nagashree, N. R. (2001). "Role of programmed cell death in development". International Review of Cytology. 202: 159–242. doi:10.1016/s0074-7696(01)02005-8. ISBN   9780123646064. ISSN   0074-7696. PMID   11061565.
  4. ↑ Saenko, SV; French, V; Brakefield, PM; Beldade, P (27 April 2008). "Conserved developmental processes and the formation of evolutionary novelties: examples from butterfly wings". Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences. 363 (1496): 1549–55. doi:10.1098/rstb.2007.2245. PMC   2615821 . PMID   18192179.
  5. ↑ Streuli, Charles H. (2009-01-15). "Integrins and cell-fate determination". Journal of Cell Science. 122 (2): 171–177. doi: 10.1242/jcs.018945 . ISSN   0021-9533. PMC   2714415 . PMID   19118209.
  6. ↑ Featherstone, D. E.; Broadie, K. S. (2005-01-01), Gilbert, Lawrence I. (ed.), "2.3 - Functional Development of the Neuromusculature", Comprehensive Molecular Insect Science, Amsterdam: Elsevier, pp. 85–134, ISBN   978-0-444-51924-5 , retrieved 2021-03-22
  7. ↑ Dev Dyn 2010, 239:1315-1329. Maduro, M. F. (2010). "Cell fate specification in the C. Elegans embryo". Developmental Dynamics. 239 (5): 1315–1329. doi: 10.1002/dvdy.22233 . PMID   20108317. S2CID   14633229.
  8. ↑ Zernicka-Goetz M: First cell fate decisions and spatial patterning in the early mouse embryo. Semin Cell Dev Biol 2004, 15:563-572.Zernicka-Goetz, M. (2004). "First cell fate decisions and spatial patterning in the early mouse embryo". Seminars in Cell & Developmental Biology. 15 (5): 563–572. doi:10.1016/j.semcdb.2004.04.004. PMID   15271302.
  9. ↑ Artavanis-Tsakonas S, Rand MD, Lake RJ: Notch signaling: cell fate control and signal integration in development. Science 1999, 284:770-776.Artavanis-Tsakonas, S.; Rand, M. D.; Lake, R. J. (1999). "Notch Signaling: Cell Fate Control and Signal Integration in Development". Science. 284 (5415): 770–6. Bibcode:1999Sci...284..770A. doi:10.1126/science.284.5415.770. PMID   10221902.
  10. ↑ Schuurmans C, Guillemot F: Molecular mechanisms underlying cell fate specification in the developing telencephalon. Curr Opin Neurobiol 2002, 12:26-34.Schuurmans, C.; Guillemot, F. (2002). "Molecular mechanisms underlying cell fate specification in the developing telencephalon". Current Opinion in Neurobiology. 12 (1): 26–34. doi:10.1016/S0959-4388(02)00286-6. PMID   11861161. S2CID   27988180.
  11. ↑ Rohrschneider MR, Nance J: Polarity and cell fate specification in the control of Caenorhabditis elegans gastrulation. Dev Dyn 2009, 238:789-796. Rohrschneider, M.; Nance, J. (2009). "Polarity and cell fate specification in the control of Caenorhabditis elegans gastrulation". Developmental Dynamics. 238 (4): 789–796. doi:10.1002/dvdy.21893. PMC   2929021 . PMID   19253398.
  12. ↑ Segalen M, Bellaiche Y: Cell division orientation and planar cell polarity pathways. Semin Cell Dev Biol 2009, 20:972-977. Segalen, M.; Bellaïche, Y. (2009). "Cell division orientation and planar cell polarity pathways". Seminars in Cell & Developmental Biology. 20 (8): 972–977. doi:10.1016/j.semcdb.2009.03.018. PMID   19447051.
  13. ↑ Fazi F, Nervi C: MicroRNA: basic mechanisms and transcriptional regulatory networks for cell fate determination. Cardiovasc Res 2008, 79:553-561. Fazi, F.; Nervi, C. (2008). "MicroRNA: basic mechanisms and transcriptional regulatory networks for cell fate determination". Cardiovascular Research. 79 (4): 553–561. doi: 10.1093/cvr/cvn151 . PMID   18539629.
  14. ↑ "Multiplex mode for the LSM 9 series with Airyscan 2: fast and gentle confocal super-resolution in large volumes" (PDF).
  15. ↑ Weissman, Tamily A.; Pan, Y. Albert (February 2015). "Brainbow: New Resources and Emerging Biological Applications for Multicolor Genetic Labeling and Analysis". Genetics. 199 (2): 293–306. doi:10.1534/genetics.114.172510. ISSN   0016-6731. PMC   4317644 . PMID   25657347.
  16. ↑ Friedmann-Morvinski, Dinorah; Verma, Inder M (March 2014). "Dedifferentiation and reprogramming: origins of cancer stem cells". EMBO Reports. 15 (3): 244–253. doi:10.1002/embr.201338254. ISSN   1469-221X. PMC   3989690 . PMID   24531722.
  17. ↑ Vibert, Laura; Daulny, Anne; Jarriault, Sophie (2018). "Wound healing, cellular regeneration and plasticity: the elegans way". The International Journal of Developmental Biology. 62 (6–7–8): 491–505. doi:10.1387/ijdb.180123sj. ISSN   0214-6282. PMC   6161810 . PMID   29938761.
  18. ↑ Shohayeb B, et al. (October 2021). "Conservation of neural progenitor identity and the emergence of neocortical neuronal diversity". Seminars in Cell and Developmental Biology. 118 (118): 4–13. doi:10.1016/j.semcdb.2021.05.024. PMID   34083116. S2CID   235336596.
  19. 1 2 3 4 5 Gilbert, Scott (2006). Developmental biology (8th ed.). Sunderland, Mass.: Sinauer Associates, Inc. Publishers. pp.  53–55. ISBN   978-0-87893-250-4.
  20. 1 2 3 4 5 Gilbert, S. F. (2000). Developmental Biology (6th ed.).
  21. ↑ Whittaker, JR (Jul 1973). "Segregation during ascidian embryogenesis of egg cytoplasmic information for tissue-specific enzyme development". PNAS. 70 (7): 2096–100. Bibcode:1973PNAS...70.2096W. doi: 10.1073/pnas.70.7.2096 . PMC   433673 . PMID   4198663.
  22. 1 2 Xiong, W.; Ferrell Jr, J. (2003). "A positive-feedback-based bistable 'memory module' that governs a cell fate decision". Nature. 426 (6965): 460–465. Bibcode:2003Natur.426..460X. doi:10.1038/nature02089. PMID   14647386. S2CID   4396489.
  23. 1 2 3 4 5 Gilbert, Scott (2014). Developmental Biology (10 ed.). Sinauer Associates, Inc.
  24. ↑ Guo G, Huss M, Tong GQ, Wang C, Li Sun L, Clarke ND, Robson P: Resolution of cell fate decisions revealed by single-cell gene expression analysis from zygote to blastocyst. Dev Cell 2010, 18:675-685.Guo, G.; Huss, M.; Tong, G.; Wang, C.; Li Sun, L.; Clarke, N.; Robson, P. (2010). "Resolution of cell fate decisions revealed by single-cell gene expression analysis from zygote to blastocyst". Developmental Cell. 18 (4): 675–685. doi: 10.1016/j.devcel.2010.02.012 . PMID   20412781.
  25. ↑ Cairns JM: Development of grafts from mouse embryos to the wing bud of the chick embryo. Dev Biol 1965, 12:36-52.Cairns, J. (1965). "Development of grafts from mouse embryos to the wing bud of the chick embryo". Developmental Biology. 12 (1): 36–00. doi:10.1016/0012-1606(65)90019-9. PMID   5833110.
  26. ↑ Nakamura, Taro; Yoshizaki, Masato; Ogawa, Shotaro; Okamoto, Haruko; Shinmyo, Yohei; Bando, Tetsuya; Ohuchi, Hideyo; Noji, Sumihare; Mito, Taro (2010-09-28). "Imaging of Transgenic Cricket Embryos Reveals Cell Movements Consistent with a Syncytial Patterning Mechanism". Current Biology. 20 (18): 1641–1647. doi: 10.1016/j.cub.2010.07.044 . ISSN   0960-9822. PMID   20800488. S2CID   11443065.
  27. ↑ Lau S, Ehrismann JS, Schlereth A, Takada S, Mayer U, Jurgens G: Cell-cell communication in Arabidopsis early embryogenesis. Eur J Cell Biol 2010, 89:225-230. Lau, S.; Ehrismann, J.; Schlereth, A.; Takada, S.; Mayer, U.; Jürgens, G. (2010). "Cell-cell communication in Arabidopsis early embryogenesis". European Journal of Cell Biology. 89 (2–3): 225–230. doi:10.1016/j.ejcb.2009.11.010. PMID   20031252.
  28. ↑ Briscoe, J (2009). "Making a grade: Sonic Hedgehog signalling and the control of neural cell fate". EMBO J. 28 (5): 457–465. doi:10.1038/emboj.2009.12. PMC   2647768 . PMID   19197245.
  29. ↑ Rabajante JF, Babierra AL (January 30, 2015). "Branching and oscillations in the epigenetic landscape of cell-fate determination". Progress in Biophysics and Molecular Biology. 117 (2–3): 240–249. doi:10.1016/j.pbiomolbio.2015.01.006. PMID   25641423. S2CID   2579314.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.