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M Kerszberg

Publications and source records attributed to M Kerszberg.

7 recordsLinked to original sources
PubMed1996

Accurate reading of morphogen concentrations by nuclear receptors: a formal model of complex transduction pathways.

Signal transduction in development follows multiple, interactive, and overlapping pathways. How does this contribute to accuracy and stability? I show that a formal model of retinoic acid receptors, based on the details of their molecular biology, demonstrates striking precision and robustness while converting a graded morphogen distribution into gene transcription patterns. Thus, transcription can be reliably established in a single row of cells, despite the absence, in the model, of intercellular signalling mechanisms. The subtle interplay of two nuclear receptor types is fundamental for this achievement: one of them ubiquitous, the other controlled itself by morphogen, they act as homodimers or heterodimers, ensuring that many errors cancel out by affecting both activation and repression pathways; regulatory molecular "reservoirs" are also formed. In spite of this robustness, some shifts in gene regulation may well have interesting evolutionary consequences. These conclusions regarding precision in transduction will remain of interest whether retinoic acid turns out to be a morphogen or not, and generalize easily to other experimental situations.

Animals↗
PubMed1994

A model for reading morphogenetic gradients: autocatalysis and competition at the gene level.

How are morphogenetic gradients interpreted in terms of embryonic gene transcription patterns within a syncytium such as the Drosophila blastoderm? We propose a hypothetical model based on recent findings in the molecular biology of transcription factors. The model postulates a morphogen which is itself a spatially distributed transcription factor M or which generates a distribution of such a factor. We posit the existence of an additional, zygotically transcribed "vernier" factor V. M and V form all possible dimers: MM, MV, and VV. These are differentially translocated to the nuclei and bind with various affinities to responsive elements in the V promoter, thereby contributing to activation/inactivation of V transcription. We find four generic regimes. In order of complexity, they are as follows: (i) MM activates V; the M gradient gives rise to a sharp transcriptional boundary for V and to a secondary gradient in the concentration of protein V; (ii) MV activates V; a sharp boundary in transcription and distribution of V arises; (iii) MM and MV compete for binding; a stationary stripe of active V transcription is generated; (iv) MM and VV are in competition; a stripe of V transcription moves from one end of the embryo toward the other and may stop and/or dwindle at an intermediate position. Tentative interpretations in terms of Drosophila genes such as bicoid and hunchback are presented.

Animals↗
PubMed1994

How neurons may compute: the case of insect sexual pheromone discrimination.

Recognition of pheromone scent by male insects probably depends on analyzing the blend's composition in terms of relative concentrations of major and minor molecular components. Based on anatomical, physiological and behavioral data concerning certain moth species and the cockroach, we propose a simple, biologically plausible neural circuit which is able to perform this task reliably. The model employs oscillations as a detecting device. This principle is easily generalized to other systems. As a computational device, ratio detection may find applications in a variety of biological situations, e.g. in the olfactory system of all animals.

Animals↗
PubMed1991

Generation of synaptic noise: selective involvement of neuronal subsets.

All central neurons are subjected to continuous and random variations of their membrane potential because of "spontaneous" activity in their presynaptic afferents. This activity, which is called synaptic noise, is presumed to be responsible for the uncertainty of the input-output relation in these cells. In the Mauthner cell of teleosts, noise is mainly inhibitory, and is generated by the release of neurotransmitter in a probabilistic manner. This inhibitory activity has been studied in detail previously. Taking advantage of this understanding, we have constructed a model of the inhibitory networks and their target in order to determine the conditions required to reproduce the main stochastic aspects of synaptic noise. We have used a combination of computer simulations and simple semianalytical arguments. We conclude that, surprisingly, cells in the presynaptic networks do not contribute equally to these background fluctuations. Rather, noise is generated primarily by the operation of subsets of afferent cells: the spectrum is either dominated by signals originating from interneurons which make few terminals on the Mauthner cell, or by the output of "burster" cells firing spike trains rather than single spikes. Both possibilities lead to specific predictions, one of which has already been verified.

Analysis of Variance↗
PubMed1989

Developmental canalization can enhance species survival.

We investigate the behavior of haploid, asexual populations undergoing an evolutionary process. Each individual is endowed with a genotype, and one of several possible developmental mechanisms mapping this genotype onto a phenotype. We show that various properties of the mapping itself have important consequences for the survival of the groups. The populations which are most successful, both alone (but in a changing environment) as well as in competition against other groups (for which the mapping is different) consist of organisms where gene expression is characterized by pleiotropism, polygenic inheritance, and some amount of canalization (i.e. error damping). These same features lead to the appearance of patterns of punctuated equilibrium during evolution. Punctuated evolution was sometimes observed even in the absence of stabilizing selection; it then arose solely from the internal developmental constraints.

Adaptation, Physiological↗