Biology subjects

Kolb, M.

Publications and source records attributed to Kolb, M..

8 recordsLinked to original sources

bioRxiv2026

Before auxin distribution matters: Prepatterning of the Arabidopsis embryo axis by MPK6-dependent AUX/IAA8 phosphorylation

In growth and development of plants, the signaling molecule auxin plays an instrumental role. Many patterning processes are controlled by auxin signaling in a self-organizing matter. After fertilization, such a patterning process needs to be started for the first time during plant life. Contrary to previous models, we show that the first differential auxin response that separates embryonic from extra-embryonic development in the two zygotic daughter cells happens independently of a detectable auxin gradient. Instead, differential phosphorylation of the transcriptional inhibitor Aux/IAA8 by MAP kinase signaling leads to differences in auxin sensitivity between the two daughter cells, initiating embryonic development in the apical cell. IAA8 phosphorylation in the basal cell prevents proteasomal degradation, suppressing canonical auxin responses, which initiates extra-embryonic development. MAP kinase signaling therefore precedes auxin gradients and prepatterns the apical-basal axis independently of an auxin gradient.

plant biology↗

bioRxiv2026

Biotic-response networks are an important organizer of the transcriptome in wild Arabidopsis thaliana populations

Extensive laboratory experimentation has revealed conserved molecular pathways controlling growth and stress responses in plants, yet how these programs operate in natural settings remains poorly understood. We investigated transcriptome organization in wild populations of Arabidopsis thaliana by sampling plants from 60 natural sites in Europe and North America across two seasons. Transcriptomes varied extensively among individuals and showed largely continuous rather than discrete structure across geography and season. Although disease and microbial colonization were common in the wild, wild transcriptomes did not simply recapitulate canonical laboratory stress signatures. Measured microbial infection, environmental, and phenotypic variables explained only a modest fraction of total expression variation, but infection-associated signals accounted for the largest share of the explainable component. Consistent with this, biotic-response networks defined in controlled laboratory experiments were well conserved in wild transcriptomes, whereas control and abiotic-response networks were substantially reorganized. Together, these results suggest that while core transcriptional modules remain recognizable across environments, regulatory relationships among modules differ markedly between laboratory and natural contexts. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=129 SRC="FIGDIR/small/711176v1_ufig1.gif" ALT="Figure 1"> View larger version (28K): org.highwire.dtl.DTLVardef@1c89152org.highwire.dtl.DTLVardef@bcd1acorg.highwire.dtl.DTLVardef@6975a2org.highwire.dtl.DTLVardef@1a9e2fe_HPS_FORMAT_FIGEXP M_FIG C_FIG

genomics↗

bioRxiv2024

Transport properties of canonical PIN-FORMED proteins and the role of the loop domain in auxin transport

Indole-3-acetic acid (IAA), the most abundant endogenous auxin is transported in plants in a polar fashion by PIN-FORMED (PIN) transporters and controls virtually all plant growth and developmental processes. Canonical PINs possess a long and largely disordered cytosolic loop domain which is shorter in non-canonical PINs. Auxin transport by canonical PINs is activated loop phosphorylation by kinases. While the structure of the transmembrane domains of these transporters was recently solved, their transport properties remained poorly characterized and particularly the relative roles of the transmembrane and loop domain therein. In this study we used flux studies to obtain quantitative kinetic parameters of IAA transport mediated by canonical PINs as well as of chimeras between transmembrane and loop domains of different PINs upon their activation by D6 PROTEIN KINASE or PINOID. We found that the transporters possess distinct transport properties that are due to both the transmembrane and loop domain. To demonstrate the physiological relevance of these distinct transport properties, we modelled root tip IAA distribution patterns and investigated the potential of different PINs to complement the agravitropic root growth phenotype of the pin2 mutant when expressed in the PIN2 domain. We found a strong correlation between transport parameters and physiological output indicating that in addition to PIN polarity a low transport rate in the PIN2 expression domain is required for gravitropic growth. Overall, the data show that the loop domain is not only required for activation of PIN-mediated auxin transport but has an additional role in the transport cycle by a currently unknown mechanism.

plant biology↗

bioRxiv2023

Defective mesenchymal Bmpr1a-mediated BMP signaling causes congenital pulmonary cysts

Abnormal lung development can cause congenital pulmonary cysts, the mechanisms of which remain largely unknown. Although the cystic lesions are believed to result directly from disrupted airway epithelial cell growth, the extent to which developmental defects in lung mesenchymal cells contribute to abnormal airway epithelial cell growth and subsequent cystic lesions has not been thoroughly examined. In the present study, we dissected the roles of BMP receptor 1a (Bmpr1a)- mediated BMP signaling in lung mesenchyme during prenatal lung development and discovered that abrogation of mesenchymal Bmpr1a disrupted normal lung branching morphogenesis, leading to the formation of prenatal pulmonary cystic lesions. Severe deficiency of airway smooth muscle cells and subepithelial elastin fibers were found in the cystic airways of the mesenchymal Bmpr1a knockout lungs. In addition, ectopic mesenchymal expression of BMP ligands and airway epithelial perturbation of the Sox2-Sox9 proximal-distal axis were detected in the mesenchymal Bmpr1a knockout lungs. However, deletion of Smad1/5, two major BMP signaling downstream effectors, from the lung mesenchyme did not phenocopy the cystic abnormalities observed in the mesenchymal Bmpr1a knockout lungs, suggesting that a Smad-independent mechanism contributes to prenatal pulmonary cystic lesions. These findings reveal for the first time the role of mesenchymal BMP signaling in lung development and a potential pathogenic mechanism underlying congenital pulmonary cysts.

developmental biology↗

bioRxiv2023

High versatility to meet conservation targets for biodiversity and hydrological services at the Riviera Maya, Quintana Roo, Mexico

The ecosystem services (ES) framework has been proposed as an alternative to face the multiple challenges presented by biodiversity conservation, but the spatial conservation priorities of ES have been found to show low concordance levels with areas of high importance for biodiversity, which can lead to conflict during reserve design. To address this problem, the use of quantitative methods derived from systematic conservation planning has been proposed to identify spatial solutions that achieve the simultaneous representation of both elements in a spatially efficient manner. The aim of this study is to evaluate the differences between priority sites for biodiversity and hydrological ecosystem services (HES) using spatial prioritization models and to identify opportunities for co-benefits that allow an efficient conservation planning proposal, using as a case study the Riviera Maya, Mexico. The following hypothesis were tested by comparing models based on the prioritization algorithm Marxan: (1) Priority sites for biodiversity and HES are different, (2) HES priority sites adequately represent biodiversity conservation targets, and (3) integrating HES and biodiversity into one model is more efficient for representing conservation targets than combining the individual models for both elements. The results confirm: (1) Biodiversity and HES priority sites have different spatial patterns, sharing only 24% of priority sites, (2) HES priority sites achieve a high percentage (95%) of biodiversity conservation targets, showing that they can potentially be used for biodiversity representation, and (3) integrating HES and biodiversity into one model is more efficient to represent conservation targets than considering both elements individually (46% vs 66% of the study area). As there are no irreplaceable sites for biodiversity conservation, and less than 8% of the study area is covered by protected areas, there are clearly opportunities to align biodiversity and HES conservation actions at the Riviera Maya, Mexico. Despite the high context dependency of the spatial distribution of priority sites for biodiversity and HES, this study shows that the integration of conservation targets of both in the planning process can provide a solution to represent a high number of biodiversity and HES conservation targets.

systems biology↗

bioRxiv2021

GraviKit: an easy-to-implement microscope add-on for observation of gravitation dependent processes

One of the most important environmental cues for living organisms is gravity and many developmental processes depend on it. However, when it comes to light microscopy, a majority of studies on these processes work with their objects of interest placed perpendicular to their natural orientation. One reason for that is probably that light microscopes with the required horizontal beampath are either costly or require advanced technical skills. To circumvent these obstacles and make imaging of gravity-dependent processes with a horizontal beampath possible for any lab we developed GraviKit. It converts a standard inverted research microscope into an imaging device with a horizontal beampath with a stage that rotates the sample around the optical axis. Like this, the direction of gravity can be freely chosen during an imaging experiment. The system is easy to implement and suitable for multi-user environments.

developmental biology↗

bioRxiv2020

Inhalation: A means to explore and optimize nintedanib's pharmacokinetic/pharmacodynamic relationship

Oral nintedanib is marketed for the treatment of idiopathic pulmonary fibrosis (IPF). While effective slowing fibrosis progression, as an oral medicine nintedanib is limited. To reduce side effects and maximize efficacy, nintedanib was reformulated as a solution for nebulization and inhaled administration. To predict effectiveness treating IPF, the nintedanib pharmacokinetic/pharmacodynamic relationship was dissected. Pharmacokinetic analysis indicated oral-delivered nintedanib plasma exposure and lung tissue partitioning were not dose-proportional and resulting lung levels were substantially higher than blood. Although initial-oral absorbed nintedanib efficiently partitioned into the lung, only a quickly eliminated fraction appeared available to epithelial lining fluid (ELF). Because IPF disease appears to initiate and progress near the epithelial surface, this observation suggests short duration nintedanib exposure (oral portion efficiently partitioned to ELF) is sufficient for IPF efficacy. To test this hypothesis, exposure duration required for nintedanib activity was explored. In vitro, IPF-cellular matrix (IPF-CM) increased primary normal human fibroblast (nHLF) aggregate size and reduced nHLF cell count. IPF-CM also increased nHLF ACTA2 and COL1A expression. Whether short duration (inhalation mimic) or continuous exposure (oral mimic), nintedanib (1-100 nM) reversed these effects. In vivo, intubated silica produced a strong pulmonary fibrotic response. Once-daily (QD) 0.021, 0.21 and 2.1 mg/kg intranasal (IN; short duration inhaled exposure) and twice daily (BID) 30 mg/kg oral (PO; long duration oral exposure) showed that at equivalent-delivered lung concentrations, QD short duration inhaled nintedanib exposure (0.21 mg/kg IN vs. 30 mg/kg PO) exhibited equivalent-to-superior activity as BID oral (reduced silica-induced elastance, alpha-smooth muscle actin, interleukin-1 beta (IL-1{beta}) and soluble collagen, and lung macrophage and neutrophils). An increased lung dose (2.1 mg/kg IN vs. 30 mg/kg PO) exhibited increased effect by further reducing silica-induced elastance, IL-1{beta} and soluble collagen. Neither oral nor inhaled nintedanib reduced silica-induced parenchymal collagen. Both QD inhaled and BID oral nintedanib reduced silica-induced inflammatory index with oral achieving significance. In summary, nintedanib pulmonary anti-fibrotic activity can be achieved using small, infrequent inhaled doses to deliver oral equivalent-to-superior therapeutic effect.

pharmacology and toxicology↗

bioRxiv2019

FK506-binding protein 13 expression is upregulated in interstitial lung disease and correlated with clinical severity: a potentially protective role.

Pulmonary fibrosis is a progressive lung disease characterized by myofibroblast accumulation and excessive extracellular matrix deposition. Endoplasmic reticulum (ER) stress initiates the unfolded protein response (UPR), a cellular stress response pathway that has been implicated in both inflammatory and fibrotic processes. Here, we sought to investigate the role of the 13 kDa FK506-binding protein (FKBP13), an ER stress-inducible molecular chaperone, in various forms of pulmonary fibrosis. We first characterized the gene and protein expression of FKBP13 in lung biopsy samples from 24 patients with idiopathic pulmonary fibrosis (IPF) and 17 control subjects. FKBP13 expression was found to be elevated in the fibrotic regions of IPF lung tissues, and within this cohort, was correlated with declining forced vital capacity and dyspnea severity. FKBP13 expression was also increased in lung biopsies of patients with hypersensitivity pneumonitis, rheumatoid arthritis, and sarcoidosis-associated interstitial lung disease. We next evaluated the role of this protein using FKBP13-/- mice in a bleomycin model of pulmonary fibrosis. Animals were assessed for lung function and histopathology at different stages of lung injury including the inflammatory (Day 7), fibrotic (Day 21) and resolution (Day 50) phase. FKBP13-/- mice showed increased infiltration of inflammatory cells and cytokines at Day 7, increased lung elastance and fibrosis at Day 21, and impaired resolution of fibrosis at Day 50. These changes were associated with an increased number of cells that stained positive for TUNEL and cleaved caspase 3 in the FKBP13-/- lungs, indicating a heightened cellular sensitivity to bleomycin. Our findings suggest that FKBP13 is a potential biomarker for severity or progression of interstitial lung diseases, and that it has a biologically relevant role in protecting mice against bleomycin-induced injury, inflammation and fibrosis.

pathology↗