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Weijers, D.

Publications and source records attributed to Weijers, D..

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Maternal inflammation significantly impacts cortical interneuron development in a subtype-specific manner

Severe infections during pregnancy are one of the major risk factors for cognitive brain impairment in offspring. It has been suggested that maternal inflammation leads to dysfunction of cortical GABAergic interneurons that in turn underlies cognitive impairment of the affected offspring. However, the evidence comes largely from studies of adult or mature brain and how impairment of inhibitory circuits arises upon maternal inflammation is unknown. Here we show that maternal inflammation affects multiple steps of cortical GABAergic interneuron development, i.e. proliferation of precursor cells, migration and positioning of neuroblasts as well as neuronal maturation. Importantly, the development of distinct subtypes of cortical GABAergic interneurons was discretely impaired as a result of maternal inflammation. This translated into a reduction in cell numbers, redistribution across cortical regions and layers, changes in morphology and cellular properties. Furthermore, selective vulnerability of GABAergic interneuron subtypes was associated with the stage of brain development. Thus, we propose that maternally-derived insults have developmental stage-dependent effects which contribute to the complex etiology of cognitive impairment in the affected offspring.

neuroscience

OsIQD14 regulates rice grain shape through modulating the microtubule cytoskeleton

Cortical microtubule (MT) arrays play a critical role in plant cell shape determination by defining the direction of cell expansion1-3. The control of plant organ shape and architecture is a major target of cereal crop improvement. Given the pleiotropic effects of MT modification, however, it is challenging to exploiting MT array organization for crop improvement. Moreover, as plants continuously adapt cell growth and expansion to ever-changing environmental conditions, multiple environmental (e.g. light4) and developmental (e.g. hormones5,6) inputs need to be translated into changes of the MT cytoskeleton. Here, we identify and functionally characterize an auxin-inducible and MT-localized protein OsIQ67-DOMAIN14 (OsIQD14), which is highly expressed in rice seed hull cells. While deficiency of OsIQD14 results in short and wide seeds and increases overall yield, overexpression leads to narrow and long seeds, caused by changes in the direction of MT arrangement. We further show that OsIQD14-mediated MT reordering is regulated through interacting with SPIRAL2, a MT-binding protein involved in KATANIN1-mediated MT rearrangement7,8, and with calmodulin proteins. As such, OsIQD14 acts as an integrator of auxin and calcium inputs into MT rearrangements, and allows effective local cell shape manipulation to improve a key rice yield trait.

plant biology

IQD proteins integrate auxin and calcium signaling to regulate microtubule dynamics during Arabidopsis development

Geometry and growth and division direction of individual cells are major contributors to plant organ shape and these processes are dependent on dynamics of microtubules (MT). Different MT structures, like the cortical microtubules, preprophase band and mitotic spindle, are characterized by diverse architectural dynamics (Hashimoto, 2015). While several MT binding proteins have been identified that have various effects on MT stability and architecture, they do not discriminate between the different MT structures. It is therefore likely that specific MT binding proteins exist that differentiate between MT structures in order to allow for the differences in architectural dynamics. Although evidence for the effect of specific cues, such as light and auxin, on MT dynamics has been shown in recent years (Lindeboom et al., 2013; Chen et al., 2014), it remains unknown how such cues are integrated and lead to specific effects. Here we provide evidence for how auxin and calcium signaling can be integrated to modulate MT dynamics, by means of IQD proteins. We show that the Arabidopsis IQD15-18 subclade of this family is regulated by auxin signaling, can bind calmodulins in a calcium-dependent manner and are evolutionarily conserved. Furthermore, AtIQD15-18 directly bind SPIRAL2 protein in vitro and in vivo and modulate its function, likely in a calmodulin-dependent way, thereby providing a missing link between two important regulatory pathways of MT dynamics.\n\nOne sentence summaryIQD proteins integrate auxin and calcium signaling, two major signaling pathways, to control the cytoskeleton dynamics and cell shape of Arabidopsis.

plant biology

A microtubule-based mechanism predicts cell division orientation in plant embryogenesis

Oriented cell divisions are significant in plant morphogenesis because plant cells are embedded in cell walls and cannot relocate. Cell divisions follow various regular orientations, but the underlying mechanisms have not been clarified. We show that cell-shape dependent self-organisation of cortical microtubule arrays is crucial for determining planes of early tissue-generating divisions and forms the basis for robust control of cell division orientation in the embryo. To achieve this, we simulate microtubules on actual cell surface shapes from which we derive a minimal set of three rules for proper array orientation. The first rule captures the effects of cell shape alone on microtubule organisation, the second rule describes the regulation of microtubule stability at cell edges and the third rule includes the differential effect of auxin on local microtubule stability. These rules explain early embryonic division plane orientations and offer a framework for understanding patterned cell divisions in plant morphogenesis.

developmental biology

Origin and evolution of the nuclear auxin response system

The small signaling molecule auxin controls numerous developmental processes in land plants, acting mostly by regulating gene expression. Auxin response proteins are represented by large families of diverse functions, but neither their origin nor their evolution is understood. Here we use a deep phylogenomics approach to reconstruct both the origin and the evolutionary trajectory of all nuclear auxin response protein families. We found that, while all subdomains are ancient, a complete auxin response mechanism is limited to land plants. Functional phylogenomics predicts defined steps in the evolution of response system properties, and comparative transcriptomics across six ancient lineages revealed how these innovations shaped a sophisticated response mechanism. Genetic analysis in a basal land plant revealed unexpected contributions of ancient non-canonical proteins in auxin response as well as auxin-unrelated function of core transcription factors. Our study provides a functional evolutionary framework for understanding diverse functions of the auxin signal.

genomics

An Inference Approach Combines Spatial And Temporal Gene Expression Data To Predict Gene Regulatory Networks In Arabidopsis Stem Cells

Identifying the transcription factors (TFs) and associated networks involved in stem cell regulation is key for understanding the initiation and growth of plant tissues and organs. Although many TFs have been shown to have a role in the Arabidopsis root stem cells, a comprehensive view of the transcriptional signature of the stem cells is lacking. In this work, we used spatial and temporal transcriptomic data to predict interactions among the genes involved in stem cell regulation. For this, we transcriptionally profiled several stem cell populations and developed a gene regulatory network (GRN) inference algorithm that combines clustering with Dynamic Bayesian Network (DBN) inference. We leveraged the topology of our networks to infer potential key regulators. The results presented in this work show that our combination of molecular biology approaches, computational biology and mathematical modeling was key to identify candidate factors that function in the stem cells. Specifically, through experimental validation and mathematical modeling, we identified PERIANTHIA (PAN) as an important molecular regulator of quiescent center (QC) function.

plant biology

Auxin Response Factors -- output control in auxin biology

The phytohormone auxin is involved in almost all developmental processes in land plants. Most, if not all, of these processes are mediated by changes in gene expression. Auxin acts on gene expression through a short nuclear pathway that converges upon the activation of a family of DNA-binding transcription factors. These AUXIN RESPONSE FACTORS (ARFs) are thus the effector of auxin response and translate the chemical signal to the regulation of a defined set of genes. Given the limited number of dedicated components in auxin signaling, distinct properties among the ARF family likely contributes to the establishment of multiple unique auxin responses in plant development. In the two decades following the identification of the first ARF in Arabidopsis much has been learnt about how these transcription factors act, and how they generate unique auxin responses. Progress in genetics, biochemistry, genomics and structural biology have helped to develop mechanistic models for ARF action. However, despite intensive efforts, many central questions are yet to be addressed. In this review we highlight what has been learnt about ARF transcription factors, and identify outstanding questions and challenges for the near future.

plant biology

Regulation of intercellular TARGET OF MONOPTEROS 7 protein transport in the Arabidopsis root

Intercellular communication coordinates hypophysis establishment in the Arabidopsis embryo. Previously, TARGET OF MONOPTEROS 7 (TMO7) was reported to be transported to the hypophysis, the founder cell of the root cap, and RNA suppression experiment implicated its function in embryonic root development. However, it remained unclear what protein properties and mechanisms mediate TMO7 protein transport, and what role the movement plays in development. Here, we report that in the post-embryonic root, TMO7 and its close relatives are transported into the root cap through plasmodesmata in a sequence, but not size dependent manner. We also show that nuclear residence is critical for TMO7 transport, and postulate that modification, potentially phosphorylation, labels TMO7 for transport. Additionally, three novel CRISPR/Cas9-induced tmo7 alleles confirmed a role in hypophysis division, but suggest complex redundancies with close relatives in root formation. Finally, we demonstrate that TMO7 transport is biologically meaningful, as local expression partially restores hypophysis division in a plasmodesmatal protein transport mutant. Our study identifies motifs and amino acids critical for TMO7 protein transport and establishes the importance of TMO7 in hypophysis and root development.\n\nSummary StatementUnique protein motifs, subcellular localization and post-translational modification, rather than protein size regulate plasmodesmatal transport of TMO7 family proteins during Arabidopsis root development.

plant biology