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Cellular retinoic acid-binding protein 1 (CRABP1) binds retinoic acid (RA) specifically in the cytoplasm with unclear functions. CRABP1 is highly and specifically expressed in spinal motor neurons (MNs). Clinical and pre-clinical data reveal a potential link between CRABP1 and MN diseases, including the amyotrophic lateral sclerosis (ALS). We established a sequenced MN-muscle co-differentiation system to engineer an in vitro functional 3D NMJ model for molecular studies and demonstrated that CRABP1 in MNs contributes to NMJ formation and maintenance. Consistently, Crabp1knockout (CKO) mice exhibited an adult-onset ALS-like phenotype with progressively deteriorated NMJs, characterized with behavioral, EchoMRI, electrophysiological, histological, and immunohistochemical studies at 2–20-months old. Mechanistically, CRABP1 suppresses CaMKII activation to regulate neural Agrnexpression and downstream muscle LRP4-MuSK signaling, thereby maintaining NMJ. A proof-of-concept was provided by specific re-expression of CRABP1 to rescue Agrnexpression and the phenotype. This study identifies CRABP1-CaMKII-Agrnsignaling as a physiological pre-synaptic regulator in the NMJ. This study also highlights a potential protective role of CRABP1 in the progression of NMJ deficits in MN diseases.

With strong light–matter interaction in their atomically thin layered structures, two-dimensional (2D) materials have been widely investigated for optoelectronic applications such as photodetectors and photovoltaic devices. Depending on the aim of optoelectronic applications, different device structures have been employed. Lateral phototransistor structures have been employed for high optical gain, while vertical photodiode structures have been employed for fast response and low power operation. Herein, we demonstrate a multimodal photodetector platform based on 2D materials, combining both a phototransistor and a photodiode and taking the corresponding desirable characteristics from each structure within a single device. In this platform, a multilayered transition-metal dichalcogenide flake is transferred on top of metal electrodes, and a transparent gate electrode is employed. The channel region of the flake between electrodes operates as a phototransistor providing a high gain mode, while the electrode region in the same flake operates as a vertical Schottky photodiode providing a fast response mode. These modes can be dynamically selected by controlling the drain voltage and gate voltage.