Evolutionary change in the functional specificity of genes

Species throughout the animal kingdom share not only housekeeping but also many key regulatory genes. Nonetheless, species differ from one another developmentally and thus, also morphologically. One of the general aims of comparative developmental genetics is to understand how similar molecules can generate the known diversity of biological form. Here, we argue that gene function can change in different ways during the evolution of developmental processes. Genes can be recruited to serve completely new functions in a new regulatory linkage (co-option), they can change their molecular specificity while remaining in the original (homologous) developmental program and can, at the same time, retain other functions. We describe evidence for such evolutionary patterns based on the comparison of loss-of-function mutations of homologous genes of the two free-living nematodes Caenorhabditis elegans and Pristionchus pacificus. Ultimately, it is the interplay of conservation and change of the specificity of genes and genetic networks that generates developmental novelty over evolutionary time

A phylogenetic interpretation of nematode vulval variations

Over the last few years vulva development in nematodes has been used as a model system to study the evolution of developmental processes by carrying out cell lineage and cell ablation studies in various nematodes. Furthermore, a genetic and molecular analysis of vulva development has been initiated in Pristionchus pacificus. Evolutionary interpretation of these comparative developmental studies requires a phylogenetic understanding of nematodes. Recently, a molecular phylogeny for the phylum Nematoda has been published. Here, we place the comparative data of vulva development onto this phylogeny of nematodes to infer the direction of evolutionary change

General anesthesia globally synchronizes activity selectively in layer 5 cortical pyramidal neurons

General anesthetics induce loss of consciousness, a global change in behavior. However, a corresponding global change in activity in the context of defined cortical cell types has not been identified. Here, we show that spontaneous activity of mouse layer 5 pyramidal neurons, but of no other cortical cell type, becomes consistently synchronized invivo by different general anesthetics. This heightened neuronal synchrony is aperiodic, present across large distances, and absent in cortical neurons presynaptic to layer 5 pyramidal neurons. During the transition to and from anesthesia, changes in synchrony in layer 5 coincide with the loss and recovery of consciousness. Activity within both apical and basal dendrites is synchronous, but only basal dendrites' activity is temporally locked to somatic activity. Given that layer 5 is a major cortical output, our results suggest that brain-wide synchrony in layer 5 pyramidal neurons may contribute to the loss of consciousness during general anesthesia. Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved

Learning-related plasticity in denrite-targetin layer 1 interneurons

A wealth of data has elucidated the mechasms by which sensory inputs are encoded in the neocortex, but how these processes are regulated by the behavioral relevance of sensory information is less understood. Here, we focus on neocortical layer 1 (L1), a key location for processing of such top-down information. Using Neuron-Derived Neotrophic Factor (NDNF) as a selective marker of L1 interneurons (INs) and in vivo 2-photon calcium imaging, electrophysiology, viral tracing, optogenetics, and associative memory, we find that L1 NDNF-INs mediate a prolonged form of inhbitionin distal pyramidal neuron dendrites that correlates with the strength of the memory trace. Conversely, inhibition from Martinotti cells remains unchanged after conditioning but in turn tightly controls sensory responses in NDNF-INs. These results define a genetically addressable form of dendritic inhibition that is highly experience dependent and indicate that in addition to disinibition, salient stimuli are encoded at elevated levels of distal dendritic inhibition

Pristionchus pacificus: a satellite organism in evolutionary developmental biology

Pristionchus pacificus has been described as a satellite organism, for functional comparative studies with Caenorhabditis elegans. Like C. elegans, P. pacificus is also easily cultured in the laboratory on a lawn of E. coli bacteria. P. pacificus is a hermaphroditic species with a 4-day life cycle, but unlike most nematodes which pass through four juvenile stages during their development, P. pacificus has only three juvenile stages. The combination of genetic, molecular and cell-biological studies have made P. pacificus a model system in the new field of evolutionary developmental biology. One process that has been studied in detail is the development of the vulva. Genetic and molecular studies revealed that the function of several genes involved in vulva development differs between P. pacificus and C. elegans. Here, we review our genetic and molecular studies of P. pacificus. We show that P. pacificus is well-suited as a satellite organism not only for understanding the cellular and genetic aspects of evolutionary change, but also for addressing questions of molecular evolution at the genomic level. Pristionchus pacificus wurde vor mehrerern Jahren als “Satelitten-Organism” für funktionelle-vergleichende Studien mit dem Modellorganismus C. elegans beschrieben. P. pacificus ist eine hermaphroditische Art mit einer Generationszeit von 4 Tagen und kann auf E. coli gezüchtet werden. Die Analyse des Lebenszyklus hat gezeigt dass diese Art im Gegensatz zu den meisten Nematoden nur drei Juvenilstadien durchläuft. Da in P. pacificus genetische, molekular-biologische und zelluläre Methoden in ähnlicher Weise zum Einsatz kommen können wie in C. elegans, ist diese Art ein ideales Modellsystem für evolutionäre entwicklungsbiologische Fragestellungen. Ein besonders detailliert analysierter Entwicklungsprozess ist die Bildung der Vulva. Genetische und molekulare Arbeiten haben gezeigt dass einige in beiden Arten an der Vulva-Bildung beteiligte homologen Gene, sich in ihrer detaillierten Funktion deutlich voneinander unterscheiden. Die vorliegende Arbeit gibt einen Überblick über die genetischen und molekularen Aspekte der Vulva-Entwicklung in P. pacificus und zeigt die Potenzen der Art auch für zukünftige molekulare und genomische Untersuchungen

Learning-related plasticity in dendrite-targeting layer 1 interneurons

A wealth of data has elucidated the mechanisms by which sensory inputs are encoded in the neocortex, but how these processes are regulated by the behavioral relevance of sensory information is less understood. Here, we focus on neocortical layer 1 (L1), a key location for processing of such top-down information. Using Neuron-Derived Neurotrophic Factor (NDNF) as a selective marker of L1 interneurons (INs) and in vivo 2-photon calcium imaging, electrophysiology, viral tracing, optogenetics, and associative memory, we find that L1 NDNF-INs mediate a prolonged form of inhibition in distal pyramidal neuron dendrites that correlates with the strength of the memory trace. Conversely, inhibition from Martinotti cells remains unchanged after conditioning but in turn tightly controls sensory responses in NDNF-INs. These results define a genetically addressable form of dendritic inhibition that is highly experience dependent and indicate that in addition to disinhibition, salient stimuli are encoded at elevated levels of distal dendritic inhibition

Static and dynamic forces on a permanent magnet levitating between superconducting surfaces

A charged magnetic microsphere (radius 100 µm) is levitating inside a superconducting niobium capacitor. Because of its charge of about 1 pC, oscillations about the equilibrium position can be excited and detected electrically. The properties of this oscillator are investigated in order to study the static and dynamic forces of magnetic levitation. We find resonance frequencies between 200 Hz and 600 Hz. The resonance frequency and the damping are amplitude dependent due to nonlinear return forces and nonlinear friction, respectively. At small amplitudes the Q value is about 106 in vacuum. A dc field can be applied to change the equilibrium position and consequently the resonance frequency. From the data the spatial dependence of the static force and of the dynamic stiffness can be determined and an empirical relation between both is established. Quite often, we find a hysteretic behavior of the static force whereas the stiffness is a reversible function of the position. Amplitude dependent damping is observed both in the decay of the free oscillations and in the dependence of the amplitude of the forced oscillations on the driving force

Evolution of Na,K-ATPase βm-subunit into a coregulator of transcription in placental mammals

Change in gene functions (gene cooption) is one of the key mechanisms of molecular evolution. Genes can acquire new functions via alteration in properties of encoded proteins and/or via changes in temporal or spatial regulation of expression. Here we demonstrate radical changes in the functions of orthologous ATP1B4 genes during evolution of vertebrates. Expression of ATP1B4 genes is brain-specific in teleost fishes, whereas it is predominantly muscle-specific in tetrapods. The encoded βm-proteins in fish, amphibian, and avian species are β-subunits of Na,K-ATPase located in the plasma membrane. In placental mammals βm-proteins lost their ancestral functions, accumulate in nuclear membrane of perinatal myocytes, and associate with transcriptional coregulator Ski-interacting protein (SKIP). Through interaction with SKIP, eutherian βm acquired new functions as exemplified by regulation of TGF-β-responsive reporters and by augmentation of mRNA levels of Smad7, an inhibitor of TGF-β signaling. Thus, orthologous vertebrate ATP1B4 genes represent an instance of gene cooption that created fundamental changes in the functional properties of the encoded proteins