Biology subjects

Niedermoser, I.

Publications and source records attributed to Niedermoser, I..

4 recordsLinked to original sources

bioRxiv2023

Stress-induced clustering of the UPR sensor IRE1 is driven by disordered regions within its ER lumenal domain

Upon accumulation of unfolded proteins at the endoplasmic reticulum (ER), IRE1 activates the unfolded protein response (UPR) to restore protein-folding homeostasis. During ER stress, IRE1s ER lumenal domain (LD) drives its clustering on the ER membrane to initiate signaling. How IRE1s LD assembles into high-order oligomers remains largely unknown. By in vitro reconstitution experiments we show that human IRE1 LD forms dynamic biomolecular condensates. IRE1 LD condensates were stabilized when IRE1 LD was tethered to model membranes and upon binding of unfolded polypeptide ligands. Molecular dynamics simulations suggested that weak multivalent interactions are involved in IRE1 LD assemblies. Mutagenesis showed that disordered regions in IRE1 LD control its clustering in vitro and in cells. Importantly, dysregulated clustering led to defects in IRE1 signaling. Our results reveal that membranes and unfolded polypeptides act as scaffolds to assemble dynamic IRE1 condensates into stable, signaling competent clusters.

cell biology↗

bioRxiv2022

β-catenin-dependent endomesoderm specification appears to be a Bilateria-specific co-option

Endomesoderm specification based on a maternal {beta}-catenin signal and axial patterning by interpreting a gradient of zygotic Wnt/{beta}-catenin signalling was suggested to predate the split between Bilateria and their evolutionary sister Cnidaria. However, in Cnidaria, the roles of {beta}-catenin signalling in both these processes have not been proven directly. Here, by tagging the endogenous {beta}-catenin protein in the sea anemone Nematostella vectensis, we show that the oral-aboral axis in a cnidarian is indeed patterned by a gradient of {beta}-catenin signalling. Unexpectedly, in a striking contrast to Bilateria, Nematostella endoderm specification takes place opposite to the part of the embryo, where {beta}-catenin is translocated into the nuclei. This suggests that {beta}-catenin-dependent endomesoderm specification is a Bilateria-specific co-option, which may have linked endomesoderm specification with the subsequent posterior-anterior patterning.

developmental biology↗

bioRxiv2022

Sea anemone Frizzled receptors play partially redundant roles in the oral-aboral axis patterning

Canonical Wnt (cWnt) signaling is involved in a plethora of basic developmental processes such as endomesoderm specification, gastrulation and patterning the main body axis. To activate the signal, Wnt ligands form complexes with LRP5/6 and Frizzled receptors, which leads to nuclear translocation of {beta}-catenin and transcriptional response. In Bilateria, the expression of different Frizzled genes is often partially overlapping, and their functions are known to be redundant in several developmental contexts. Here we demonstrate that all four Frizzled receptors take part in the cWnt-mediated oral-aboral axis patterning in the cnidarian Nematostella vectensis but show partially redundant functions. However, we do not see evidence for their involvement in the specification of the endoderm - an earlier event likely relying on maternal, intracellular {beta}-catenin signaling components. Finally, we demonstrate that the main Wnt ligands crucial for the early oral-aboral patterning are Wnt3 and Wnt4. Comparison of our data to the knowledge from other models suggests that distinct but overlapping expression domains and partial functional redundancy of cnidarian and bilaterian Frizzled genes may represent a shared ancestral trait.

developmental biology↗

bioRxiv2020

β-catenin dependent axial patterning in Cnidaria and Bilateria uses similar regulatory logic

In animals, body axis patterning is based on the concentration-dependent interpretation of graded morphogen signals, which enables correct positioning of the anatomical structures. The most ancient axis patterning system acting across animal phyla relies on {beta}-catenin signaling, which directs gastrulation, and patterns the main body axis. However, within Bilateria, the patterning logic varies significantly between protostomes and deuterostomes. To deduce the ancestral principles of {beta}-catenin dependent axial patterning, we investigated the oral-aboral axis patterning in the sea anemone Nematostella - a member of the bilaterian sister group Cnidaria. Here we elucidate the regulatory logic by which more orally expressed {beta}-catenin targets repress more aborally expressed {beta}- catenin targets, and progressively restrict the initially global, maternally provided aboral identity. Similar regulatory logic of {beta}-catenin-dependent patterning in Nematostella and deuterostomes suggests a common evolutionary origin of these processes.

developmental biology↗