Knauer, S. | Search bioRxiv

bioRxiv2026

Specification of embryonic shoot stem cells via a small RNA-driven morphogenic circuit

The specification of embryonic stem cells capable of self-renewing and differentiation into virtually any cell type, is one of the most consequential events in the development of a multicellular organism. Yet the mechanisms establishing embryonic stem cell fate remain poorly understood, particularly in monocotyledonous cereals. Using the classic mutant leafbladeless1-raggedseedling1, we show that the small RNA tasiARF acts as a primary epidermis-derived morphogenic signal that organizes shoot stem cell specification in the maize embryo. tasiARF restricts expression of the AUXIN RESPONSE FACTOR 3 (ARF3) transcription factor, which modulates cell wall mechanics and guides the differential localization of PIN-FORMED (PIN) auxin efflux carriers, establishing a localized auxin minimum permissive for stem cell fate. Interestingly, loss of this auxin minimum and the associated shoot stem cell defects in tasiARF-deficient embryos are buffered by natural variation at a quantitative trait locus (QTL) controlling expression of MICROTUBULE-ASSOCIATED PROTEIN 65-3 (MAP65-3), a critical factor determining cell division orientation, which reshapes auxin dynamics and restores stem cell specification, and is itself under tasiARF-ARF3 control. Thus, embryonic shoot stem cell specification in maize is governed by an intricate morphogenic circuit that couples small RNA-mediated positional information to a self-stabilizing network interdependently linking cell wall mechanics, auxin signaling, and cell division patterning. This mechanistic framework reveals the redeployment of an ancient small RNA pathway as a lineage-specific innovation to establish a conserved, stem cell-permissive low auxin environment within the divergent embryonic architecture of monocotyledonous cereals. More broadly, it identifies molecular entry points for the engineering of embryogenic competence and regeneration capacity for the improvement of cereal crops.

plant biology↗

bioRxiv2020

Amyloid precursor protein causes fusion of promyelocytic leukemia nuclear bodies in human hippocampal areas with high plaque load

The amyloid precursor protein (APP) is a type I transmembrane protein with unknown physiological function but potential impact in neurodegeneration. The current study demonstrates that APP signals to the nucleus causing the generation of aggregates comprising its adapter protein FE65 and the tumour suppressor proteins p53 and PML. The PML nuclear body generation, known to be of relevance in virus defence and cell division, is induced and fusion occurs over time depending on APP signalling. We further show that the nuclear aggregates of APP C-terminal (APP-CT) fragments together with PML and FE65 are present in the aged human brain but not in cerebral organoids differentiated from iPS cells. Notably, human Alzheimers disease brains reveal a highly significant loss of these nuclear aggregates in areas with high plaque load compared to plaque-free areas of the same individual. Based on these results we conclude that APP-CT signalling to the nucleus takes place in the aged human brain and is potentially involved in the pathophysiology of AD. Taken the current knowledge on PML bodies into account, we hypothesize a new role for APP as a twofold virus response protein. The APP-dependent defence strategy includes A{beta}-virus interaction at the extracellular matrix and APP-CT driven PML aggregation in the nucleus to encapsulate the viral nucleic acid. This defence strategy preferentially occurs in high-plaque regions of the human brain and overstimulation of this pathway results in a pyrrhic victory.

neuroscience↗