Decision making during interneuron migration in the developing cerebral cortex

Appropriate interneuron migration and distribution is essential for the construction of functional neuronal circuitry and the maintenance of excitatory/inhibitory balance in the brain. GABAergic interneurons originating from ventral telencephalon choreograph a complex pattern of migration to reach their target destinations within the developing brain. This review examines the cellular and molecular underpinnings of the major decision-making steps involved in this process of oriental navigation of cortical interneurons

Nap1-Regulated Neuronal Cytoskeletal Dynamics Is Essential for the Final Differentiation of Neurons in Cerebral Cortex

SummaryThe cytoskeletal regulators that mediate the change in the neuronal cytoskeletal machinery from one that promotes oriented motility to one that facilitates differentiation at the appropriate locations in the developing neocortex remain unknown. We found that Nck-associated protein 1 (Nap1), an adaptor protein thought to modulate actin nucleation, is selectively expressed in the developing cortical plate, where neurons terminate their migration and initiate laminar-specific differentiation. Loss of Nap1 function disrupts neuronal differentiation. Premature expression of Nap1 in migrating neurons retards migration and promotes postmigratory differentiation. Nap1 gene mutation in mice leads to neural tube and neuronal differentiation defects. Disruption of Nap1 retards the ability to localize key actin cytoskeletal regulators such as WAVE1 to the protrusive edges where they are needed to elaborate process outgrowth. Thus, Nap1 plays an essential role in facilitating neuronal cytoskeletal changes underlying the postmigratory differentiation of cortical neurons, a critical step in functional wiring of the cortex

Radial Glial Dependent and Independent Dynamics of Interneuronal Migration in the Developing Cerebral Cortex

Interneurons originating from the ganglionic eminence migrate tangentially into the developing cerebral wall as they navigate to their distinct positions in the cerebral cortex. Compromised connectivity and differentiation of interneurons are thought to be an underlying cause in the emergence of neurodevelopmental disorders such as schizophrenia. Previously, it was suggested that tangential migration of interneurons occurs in a radial glia independent manner. Here, using simultaneous imaging of genetically defined populations of interneurons and radial glia, we demonstrate that dynamic interactions with radial glia can potentially influence the trajectory of interneuronal migration and thus the positioning of interneurons in cerebral cortex. Furthermore, there is extensive local interneuronal migration in tangential direction opposite to that of pallial orientation (i.e., in a medial to lateral direction from cortex to ganglionic eminence) all across the cerebral wall. This counter migration of interneurons may be essential to locally position interneurons once they invade the developing cerebral wall from the ganglionic eminence. Together, these observations suggest that interactions with radial glial scaffold and localized migration within the expanding cerebral wall may play essential roles in the guidance and placement of interneurons in the developing cerebral cortex

Single-cell transcriptomic analysis of mouse neocortical development

The development of the mammalian cerebral cortex depends on careful orchestration of proliferation, maturation, and migration events, ultimately giving rise to a wide variety of neuronal and non-neuronal cell types. To better understand cellular and molecular processes that unfold during late corticogenesis, we perform single-cell RNA-seq on the mouse cerebral cortex at a progenitor driven phase (embryonic day 14.5) and at birth—after neurons from all six cortical layers are born. We identify numerous classes of neurons, progenitors, and glia, their proliferative, migratory, and activation states, and their relatedness within and across age. Using the cell-type-specific expression patterns of genes mutated in neurological and psychiatric diseases, we identify putative disease subtypes that associate with clinical phenotypes. Our study reveals the cellular template of a complex neurodevelopmental process, and provides a window into the cellular origins of brain diseases

Developmental disruptions underlying brain abnormalities in ciliopathies

Primary cilia are essential conveyors of signals underlying major cell functions. Cerebral cortical progenitors and neurons have a primary cilium. The significance of cilia function for brain development and function is evident in the plethora of developmental brain disorders associated with human ciliopathies. Nevertheless, the role of primary cilia function in corticogenesis remains largely unknown. Here we delineate the functions of primary cilia in the construction of cerebral cortex and their relevance to ciliopathies, using an shRNA library targeting ciliopathy genes known to cause brain disorders, but whose roles in brain development are unclear. We used the library to query how ciliopathy genes affect distinct stages of mouse cortical development, in particular neural progenitor development, neuronal migration, neuronal differentiation and early neuronal connectivity. Our results define the developmental functions of ciliopathy genes and delineate disrupted developmental events that are integrally related to the emergence of brain abnormalities in ciliopathies

Hard-Loop Effective Action for Anisotropic Plasmas

We generalize the hard-thermal-loop effective action of the equilibrium quark-gluon plasma to a non-equilibrium system which is space-time homogeneous but for which the parton momentum distribution is anisotropic. We show that the manifestly gauge-invariant Braaten-Pisarski form of the effective action can be straightforwardly generalized and we verify that it then generates all n-point functions following from collisionless gauge-covariant transport theory for a homogeneous anisotropic plasma. On the other hand, the Taylor-Wong form of the hard-thermal-loop effective action has a more complicated generalization to the anisotropic case. Already in the simplest case of anisotropic distribution functions, it involves an additional term that is gauge invariant by itself, but nontrivial also in the static limit.Comment: 12 pages. Version 3: typo in (15) corrected, note added discussing metric conventions use

Direct visualization of microtubules using a genetic tool to analyse radial progenitor-astrocyte continuum in brain

Microtubule cytoskeletal dynamics of cortical progenitors and astroglial cells play critical roles in the emergence of normal functional organization of cerebral cortex and in disease processes such as tumorigenesis. However, tools to efficiently visualize these events are lacking. Here we describe a mouse genetic model to efficiently visualize and analyze radial progenitors, their astroglial progeny, and the microtubule cytoskeleton of these cells in the developing and adult brain. Using this tool, we demonstrate altered microtubule organization and capture dynamics in adenomatous polyposis coli deficient radial progenitors. Further, using multiphoton microscopy, we show the utility of this tool in real-time imaging of astrocytes in living mouse brain and the short- term stable nature of astrocytes in cerebral cortex. Thus, this model will help explore the dynamics of radial progenitor/astrocyte development or dysfunction and the influence of microtubule functions during these events

Arl13b in Primary Cilia Regulates the Migration and Placement of Interneurons in the Developing Cerebral Cortex

Coordinated migration and placement of interneurons and projection neurons lead to functional connectivity in the cerebral cortex; defective neuronal migration and the resultant connectivity changes underlie the cognitive defects in a spectrum of neurological disorders. Here we show that primary cilia play a guiding role in the migration and placement of postmitotic interneurons in the developing cerebral cortex, and that this process requires the ciliary protein, Arl13b. Through live imaging of interneuronal cilia we show migrating interneurons display highly dynamic primary cilia and we correlate cilia dynamics with the interneuron’s migratory state. We demonstrate that the guidance cue receptors essential for interneuronal migration localize to interneuronal primary cilia, but their concentration and dynamics are altered in the absence of Arl13b. Expression of Arl13b variants known to cause Joubert syndrome induce defective interneuronal migration, suggesting that defects in cilia-dependent interneuron migration may underlie the neurological defects in Joubert syndrome patients

Assimilating remote sensing data with forest growth models

As we are entering an era of increased supply of remote sensing data, we believe that dataassimilation that combines growth forecasts of previous estimates with new observations of thecurrent state has a large potential for keeping forest stand registers up to date (Ehlers et al. 2013).The data assimilation will update a forest model e in an optimal way based on the uncertainties inthe forecast and the observations, each time new data becomes available. These forecasting andupdating steps can be repeated with new available observations to get improved estimations. In thisstudy we present the first practical results from data assimilation of mean tree height, basal area andgrowing stock. The remote sensing data used were canopy height models obtained from matching ofdigital aerial photos over the test site Remningstorp in Sweden. The photos were acquired 2003,2005, 2007, 2009, 2010 and 2012 and normalized with a DEM from airborne laser scanning.The procedure for the data assimilation was as follows: mean tree height, basal area and growingstock were predicted on 18 m × 18 m raster cells using the area based method. Ten meter radiussample plots were used as field calibration data. For each photo year, the field data were adjustedfor growth to have the same state year as each acquisition year of the photos. Growth models wereconstructed from National Forest Inventory plot data. Data assimilation could then be performed onraster cell level by initially start with the estimates from 2003 year´s photos. This prediction was thenforecasted to year 2005 by calculating the growth for the raster cell. This forecasted value is thenblended with the new remote sensing estimation collected 2005. The process was then repeated forthe following years where new measurements were available. In this study, extended Kalmanfiltering was used to blend the forecasted values with the new remote sensing measurements.Validation was done for 40 m radius field plots. Further, the results were also compared with twoalternative approaches: the first was to forecast the first remote sensing estimate to the endpointand the second was to use remote sensing data acquired at the endpoint only.The preliminary results for the eight forest stands show that the variances were lower when usingassimilation of new estimates and there were less fluctuation compared to only using remote sensingdata from the endpoint. However, the mean deviation from the measured value 2011 was lowerwhen only data from the endpoint were used. The assimilated values 2011 were consistently closerto the validation data compared to only forecasting the starting estimate from 2003 to 2011