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Some recent paper and reviews


Meinhardt, H. (2015). Dorsoventral patterning by the Chordin-BMP pathway: a unified model from a pattern-formation perspective for Drosophila, vertebrates, sea urchins and Nematostella. Dev. Biol.  dx.doi.org/10.1016/j.ydbio.2015.05.025

Chordin and BMP are well preserved throughout the animal kingdom, but the functions of the components seem to be very different. Models for Chordin/BMP interactions for the DV patterning in Nematostella, sea urchins, Drosophila and vertebrates are elaborated that allow reconstructing the modifications that took place during evolution. It is shown that (1) in the evolutionary early Nematostella system the Chordin-BMP interactions acts as a pattern-forming system of activator-inhibitor type. (2) BMP obtained a second role in the generation of an antipodal signaling system; BMP is there a necessary component that fuels and is consumed by a self-enhancing reaction via pSMAD - an activator - depleted substrate pattern-forming reaction. (3) Later in evolution, Chordin and BMP became under control of other pattern-forming systems, e.g., Nodal in sea urchins; BMP became expressed complementary to Chordin. (4) In vertebrates, Chordin (with ADMP as inhibitor) became again a pattern-forming system. The model accounts for the generation of Positional Information for the DV-axis along entire AP or aboral-oral axis [Opens external link in new windowPreprint PDF]. 
 
Models for patterning primary embryonic body axes: the role of space and time
Seminars in Cell & Developmental Biology, 2015; doi:10.1016/j.semcdb.2015.06.005 [Opens external link in new windowreprint PDF]

The time-dependence of HOX gene activation of the trunk is well known. In this review, it is emphasized that gene activation under morphogen control is likewise a time-requiring process. The activation occurs stepwise; each further step requires a higher morphogen concentration and requires time. The resulting gene activation is stable against a fading of the morphogen concentration due to growth. Fate decisions are shown not to occur at delicate points of instabilities as in Waddington’s famous metaphoric ‘Epigenetic Landscape’ but by a shift from one stable gene activation to another due to a massive influence of the signaling. Self-enhancement plays a decisive role in permanent switch-like activation of genes. Mutual repression of genes makes 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’. According to these models, gene activation for brain and for trunk patterning becomes more similar than it was previously thought. 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 that were involved in asexual reproduction.
 
 
Meinhardt, H. (2012). Turing’s theory of morphogenesis of 1952 and the subsequent discovery of the crucial role of local self-enhancement and long-range inhibition. Interface Focus doi:10.1098/rsfs.2011.0097 [PDF]

In this year the one hundreds anniversary of the birthday of Alan Turing is celebrated. In an invited paper for a special issue of Interface Focus of the Roy. Soc  the basic achievements of Turing's "Theory of Chemical Basis of "Morphogenesis" are discussed. It is further shown that the requirements for pattern formation we discovered later, local self-enhancement and long-ranging inhibition, is compatible with Turing's proposal but not inherent in his paper. Knowing these conditions allowed including of non-linear and molecularly realistic interactions. Some of the more recently found realizations of pattern-forming reactions are discussed.


Meinhardt, H. (2012). Modeling pattern formation in hydra - a route to understand essential steps in development. Int. J. Dev. Biol. doi: 10.1387/ijdb.113483hm [PDF]

The paper contains an update of our modelling of pattern formation in hydra. The following elements are new:

1. Based on some experimental observation it is proposed that Wnt molecules act first as activators. After re-uptake, processing and re-secretion they are attached to small lipid particles, obtain much longer range and act in this form as inhibitors, presumably via Dkk.
This explains why no genes for long-ranging Wnt-inhibitors have been found: a particular Wnt gene codes for both. This scheme also explains why Wnt molecules has formed such a large family and why the expression patterns of the family members can lead to a “Wnt code”: each gene duplication leads to a complete pattern-forming system.
2. In addition to the Wnt - ß-cat loop there is a second cell-local Wnt3-loop, possibly involving Brachyury. This explains why the Wnt3 peak is so much sharper than the ß-catenin distribution, why the Wnt3 peaks appear with some delay during regeneration and why during budding or re-aggregation the ß-catenin distribution sharpens while the Wnt3 peak enlarges.
3. It is shown why one needs a “Pre-Head” signal during budding (possibly Wnt2) that triggers a “Pre-Foot” signal in order to achieve that the foot of the bud can emerge so closely to the head signal of the newly formed bud.

In a supplementary Powerpoint presentation animated simulations, equations, parameters and some basic programming details are provided [PowerPoint presentation]


Gierer, A. (2012). The Hydra model - a model for what? Int. J. Dev. Biol., 56, 437-445 [Opens external link in new windowPDF]
The review is an invited contribution to a special issue on the Hydra model, including personal reflections and historical aspects. Trembley’s discovery of Hydra regeneration in 1744 was the beginning of developmental biology as we understand it, providing a particularly clear model for the formation of defined patterns within initially near-uniform tissues. Recently, molecular biology has generated impressive evidence that the same types of molecules and molecular systems are involved in pattern formation in a wide range of organisms, among them coelenterates like Hydra, and thus appear to have been “invented” early in evolution. This includes the generation of spatial structures by the interplay of self-enhancing activation and “lateral” inhibitory effects of wider range. Theoretical and empirical aspects of these basic processes in development as well as the generation of biological form by tissue evagination are main topics of this review.


Meinhardt, H (2009). Models for the generation and interpretation of gradients. CSH Perspect. Biol. doi: 10.1101/cshperspect.a001362 [Opens external link in new windowlink to PDF]

This paper was written as a contribution to a book "Generation and Interpretation of Morphogen gradients" (CHS Perpectives in Biology). Among others a case is made that in many systems the relative gradient levels play a decisive role. This is in contrast to the usual assumption that only absolute concentrations are involved in the readout of gradients.
 
Meinhardt, H. (2008). Models of biological pattern formation: from elementary steps to the organization of embryonic axes. Curr. Top. Dev. Biol. 81, 1-63 [reprint PDF]
A general overview over our models is provided. The models are compared with more recent findings on the molecular level.