Max Planck Institute For Entwicklungsbiologie

Max, Germany

Max Planck Institute For Entwicklungsbiologie

Max, Germany
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Yoon W.H.,Johns Hopkins University | Meinhardt H.,Max Planck Institute For Entwicklungsbiologie | Montell D.J.,Johns Hopkins University
Nature Cell Biology | Year: 2011

Patterns of cell fates generated by morphogens are critically important for normal development; however, the mechanisms by which graded morphogen signals are converted into all-or-none cell fate responses are incompletely understood. In the Drosophila ovary, high and sustained levels of the secreted morphogen Unpaired (Upd) specify the migratory border-cell population by activating the signal transducer and activator of transcription (STAT). A lower or transient level of STAT activity specifies a non-migratory population of follicle cells. Here we identify miR-279 as a component of a feedback pathway that further dampens the response in cells with low levels of JAK/STAT activity. miR-279 directly repressed STAT, and loss of miR-279 mimicked STAT gain-of-function or loss of Apontic (Apt), a known feedback inhibitor of STAT. Apt was essential for miR-279 expression in non-migratory follicle cells, whereas another STAT target, Ken and Barbie (Ken), downregulated miR-279 in border cells. Mathematical modelling and simulations of this regulatory circuit including miR-279, Apt and Ken supported key roles for miR-279 and Apt in generating threshold responses to the Upd gradient. © 2011 Macmillan Publishers Limited. All rights reserved.


Singh A.P.,Max Planck Institute For Entwicklungsbiologie | Nusslein-Volhard C.,Max Planck Institute For Entwicklungsbiologie
Current Biology | Year: 2015

Colour patterns are prominent features of many animals and have important functions in communication, such as camouflage, kin recognition and mate choice. As targets for natural as well as sexual selection, they are of high evolutionary significance. The molecular mechanisms underlying colour pattern formation in vertebrates are not well understood. Progress in transgenic tools, in vivo imaging and the availability of a large collection of mutants make the zebrafish (Danio rerio) an attractive model to study vertebrate colouration. Zebrafish display golden and blue horizontal stripes that form during metamorphosis as mosaics of yellow xanthophores, silvery or blue iridophores and black melanophores in the hypodermis. Lineage tracing revealed the origin of the adult pigment cells and their individual cellular behaviours during the formation of the striped pattern. Mutant analysis indicated that interactions between all three pigment cell types are required for the formation of the pattern, and a number of cell surface molecules and signalling systems have been identified as mediators of these interactions. The understanding of the mechanisms that underlie colour pattern formation is an important step towards deciphering the genetic basis of variation in evolution. © 2015 Elsevier Ltd. All rights reserved.


Meinhardt H.,Max Planck Institute For Entwicklungsbiologie
Seminars in Cell and Developmental Biology | Year: 2015

Models for the generation and interpretation of spatial patterns are discussed. Crucial for these processes is an intimate link between self-enhancing and antagonistic reactions. For spatial patterning, long-ranging antagonistic reactions are required that restrict the self-enhancing reactions to generate organizing regions. Self-enhancement is also required for a permanent switch-like activation of genes. This self-enhancement is antagonized by the mutual repression of genes, making sure that in a particular cell only one gene of a set of possible genes become activated - a long range inhibition in the 'gene space'. The understanding how the main body axes are initiated becomes more straightforward if the evolutionary ancestral head/brain pattern and the trunk pattern is considered separately. To activate a specific gene at particular concentration of morphogenetic gradient, observations are compatible with a systematic and time-requiring 'promotion' from one gene to the next until the local concentration is insufficient to accomplish a further promotion. The achieved determination is stable against a fading of the morphogen, as required to allow substantial growth. Minor modifications lead to a purely time-dependent activation of genes; both mechanisms are involved to pattern the anteroposterior axis. A mutual activation of cell states that locally exclude each other accounts for many features of the segmental patterning of the trunk. A possible scenario for the evolutionary invention of segmentation is discussed that is based on a reemployment of interactions involved in asexual reproduction. © 2015 Elsevier Ltd.


Conserved from Cnidarians to vertebrates, the dorsoventral (DV) axis is patterned by the Chordin-BMP pathway. However, the functions of the pathway's components are very different in different phyla. By modeling it is shown that many observations can be integrated by the assumption that BMP, acting as an inhibitory component in more ancestral systems, became a necessary and activating component for the generation of a secondary and antipodal-located signaling center. The different realizations seen in vertebrates, Drosophila, sea urchins and Nematostella allow reconstruction of a chain of modifications during evolution. BMP-signaling is proposed to be based on a pattern-forming reaction of the activator-depleted substrate type in which BMP-signaling acts via pSmad as the local self-enhancing component and the depletion of the highly mobile BMP-Chordin complex as the long-ranging antagonistic component. Due to the rapid removal of the BMP/Chordin complex during BMP-signaling, an oriented transport and "shuttling" results, although only ordinary diffusion is involved. The system can be self-organizing, allowing organizer formation even from near homogeneous initial situations. Organizers may regenerate after removal. Although connected with some losses of self-regulation, for large embryos as in amphibians, the employment of maternal determinants is an efficient strategy to make sure that only a single organizer of each type is generated. The generation of dorsoventral positional information along a long-extended anteroposterior (AP) axis cannot be achieved directly by a single patch-like organizer. Nature found different solutions for this task. Corresponding models provide a rationale for the well-known reversal in the dorsoventral patterning between vertebrates and insects. © 2015 Elsevier Inc.


Singh A.P.,Max Planck Institute For Entwicklungsbiologie | Schach U.,Max Planck Institute For Entwicklungsbiologie | Nusslein-Volhard C.,Max Planck Institute For Entwicklungsbiologie
Nature cell biology | Year: 2014

Colour patterns are a striking feature of animals; they evolve rapidly and play an important role in natural as well as sexual selection. It has been proposed that colour pattern formation in adult vertebrates depends on Turing-type interactions between pigment cells; however, little is known about the actual developmental mechanisms underlying the complex and prolonged ontogeny of this important adult feature. Zebrafish (Danio rerio) owe their name to a repetitive pattern of dark stripes and light interstripes parallel to the anteroposterior body axis that develop during juvenile stages. By inducible Cre/loxP-mediated recombination in neural-crest-derived progenitors, we created labelled clones of skin pigment cells that were imaged over several weeks in juvenile and adult fish. Metamorphic iridophores arise from postembryonic stem cells located at the dorsal root ganglia of the peripheral nervous system. They emerge in the skin at the horizontal myoseptum to form the first interstripe and proliferate while spreading bidirectionally along the dorsoventral axis. Patterned aggregation of iridophores during their dispersal generates a series of interstripes that define the stripe regions. Melanophore progenitors appear in situ in the presumptive stripe region where they melanize and expand in size to form compact stripes. Thus, although depending on mutual interactions between different pigment cells, stripes and interstripes are formed by a completely different cellular route.


Meinhardt H.,Max Planck Institute For Entwicklungsbiologie
International Journal of Developmental Biology | Year: 2012

Modeling of pattern formation in hydra has revealed basic mechanisms that underlie the reproducible generation of complex and self-regulating patterns. Organizing regions can be generated by a local self-enhancing reaction that is coupled with an inhibitory effect of longer range. Such reactions enable pattern formation even in an initially almost homogeneous assembly of cells. A long-ranging feedback of the organizer onto the competence to perform the pattern-forming reaction stabilizes the polar axial pattern during growth and allows for regeneration with preserved polarity. Hypostome formation is assumed to be under the control of two positive feedback loops in which Wnt3 is a common element. In addition to the well-established loop employing b-catenin, a second cell-local loop is involved, possibly with Brachyury as an additional component. This model accounts for the different expression patterns of β-catenin and Wnt3. Wnt molecules are proposed to play a dual role, functioning as activators and, after processing, as inhibitors. Since Wnt genes code for complete pattern-forming systems, gene duplication and diversification lead to a family of genes whose expression regions have a precise relation to each other. Tentacle formation is an example of positioning a second pattern-forming system by medium-ranging activation and local exclusion exerted by the primary system. A model for bud formation suggests that a transient pre-bud signal is involved that initiates the formation of the foot of the bud, close to the normal foot, as well as close to the bud tip. Many dynamic regulations, as observed in classical and molecular observations, are reproduced in computer simulations. A case is made that hydra can be regarded as a living fossil, documenting an evolutionary early axis formation before trunk formation and bilaterality were invented. Animated simulations are available in the supplementary information accompanying this paper. © UBC Press.


In his pioneering work, Alan Turing showed that de novo pattern formation is possible if two substances interact that differ in their diffusion range. Since then, we have shown that pattern formation is possible if, and only if, a self-enhancing reaction is coupled with an antagonistic process of longer range. Knowing this crucial condition has enabled us to include nonlinear interactions, which are required to design molecularly realistic interactions. Different reaction schemes and their relation to Turing's proposal are discussed and compared with more recent observations on the molecular-genetic level. The antagonistic reaction may be accomplished by an inhibitor that is produced in the activated region or by a depletion of a component that is used up during the self-enhancing reaction. The autocatalysis may be realized by an inhibition of an inhibition. Activating molecules can be processed into molecules that have an inhibiting function; patterning of the Wnt pathway is proposed to depend on such a mechanism. Three-component systems, as discussed in Turing's paper, are shown to play a major role in the generation of highly dynamic patterns that never reach a stable state. © 2012 The Royal Society.


Mahalwar P.,Max Planck Institute For Entwicklungsbiologie | Walderich B.,Max Planck Institute For Entwicklungsbiologie | Singh A.P.,Max Planck Institute For Entwicklungsbiologie | Volhard C.N.,Max Planck Institute For Entwicklungsbiologie
Science | Year: 2014

The pattern of alternating blue and golden stripes displayed by adult zebrafish is composed of three kinds of pigment cells: black melanophores, yellow xanthophores, and silvery-blue iridophores. We analyzed the dynamics of xanthophores during stripe morphogenesis in vivo with long-term time-lapse imaging. Larval xanthophores start to proliferate at the onset of metamorphosis and give rise to adult xanthophores covering the flank before the arrival of stem-cell-derived iridophores and melanophores. Xanthophores compact to densely cover the iridophores forming the interstripe, and they acquire a loose stellate shape over the melanophores in the stripes. Thus, xanthophores, attracted by iridophores and repelling melanophores, sharpen and color the pattern. Variations on these cell behaviors may contribute to the generation of color pattern diversity in fish.


Singh A.P.,Max Planck Institute For Entwicklungsbiologie | Schach U.,Max Planck Institute For Entwicklungsbiologie | Nusslein-Volhard C.,Max Planck Institute For Entwicklungsbiologie
Nature Cell Biology | Year: 2014

Colour patterns are a striking feature of animals; they evolve rapidly and play an important role in natural as well as sexual selection. It has been proposed that colour pattern formation in adult vertebrates depends on Turing-type interactions between pigment cells; however, little is known about the actual developmental mechanisms underlying the complex and prolonged ontogeny of this important adult feature. Zebrafish (Danio rerio) owe their name to a repetitive pattern of dark stripes and light interstripes parallel to the anteroposterior body axis that develop during juvenile stages. By inducible Cre/loxP-mediated recombination in neural-crest-derived progenitors, we created labelled clones of skin pigment cells that were imaged over several weeks in juvenile and adult fish. Metamorphic iridophores arise from postembryonic stem cells located at the dorsal root ganglia of the peripheral nervous system. They emerge in the skin at the horizontal myoseptum to form the first interstripe and proliferate while spreading bidirectionally along the dorsoventral axis. Patterned aggregation of iridophores during their dispersal generates a series of interstripes that define the stripe regions. Melanophore progenitors appear in situ in the presumptive stripe region where they melanize and expand in size to form compact stripes. Thus, although depending on mutual interactions between different pigment cells, stripes and interstripes are formed by a completely different cellular route. © 2014 Macmillan Publishers Limited. All rights reserved.


Nusslein-Volhard C.,Max Planck Institute For Entwicklungsbiologie
Development (Cambridge) | Year: 2012

In December 1996, a special issue of Development appeared that presented in 37 papers the results of two large screens for zebrafish mutants performed in Tübingen and Boston. The papers describe about 1500 mutations in more than 400 new genes involved in a wide range of processes that govern development and organogenesis. Up to this day, the mutants provide a rich resource for many laboratories, and the issue significantly augmented the importance of zebrafish as vertebrate model organism for the study of embryogenesis, neuronal networks, regeneration and disease. This essay relates a personal account of the history of this unique endeavor. © 2012. Published by The Company of Biologists Ltd.

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