Biology subjects

Masudi, T.

Publications and source records attributed to Masudi, T..

4 recordsLinked to original sources

bioRxiv2026

Deep anatomical and ultrastructural classification of neurons in the zebrafish olfactory bulb

Neuronal circuits in the olfactory bulb (OB) perform computations fundamental to pattern classification including a decorrelation and normalization of odor-evoked activity. These computations are mediated by diverse interneurons but a comprehensive picture of interneuron types and their microcircuit organization is lacking. We provide a deep anatomical classification of neuron types and their synaptic connectivity in the OB of adult zebrafish, a well-established model to analyze olfactory computations. We reconstructed 459 neurons in an image volume acquired by serial block face scanning electron microscopy and defined 13 neuron classes based on morphological and ultrastructural features. These comprised two classes of projection neurons and 11 interneuron classes, some of which were further separated into subclasses. Ultrastructural information including spine shape, variations in neurite diameter and synaptic arrangements contributed significantly to the distinction of cell types. As in other species, reciprocal synaptic connections were abundant. Targeted synapse annotation revealed systematic connectivity between projection neurons and interneurons. These included microcircuit motifs combining reciprocal and unidirectional connectivity that provide possible structural substrates for gain control and lateral inhibition. The results provide detailed insights into the structural organization of the OB and an anatomical foundation for physiological and computational studies of information processing in olfaction.

neuroscience↗

bioRxiv2023

The Alk receptor tyrosine kinase regulates Sparkly, a novel activity regulating neurosecretory protein in the Drosophila CNS.

Numerous roles for the Alk receptor tyrosine kinase have been described in Drosophila, including functions in the central nervous system (CNS), however the molecular details are poorly understood. To gain mechanistic insight, we employed Targeted DamID (TaDa) transcriptional profiling to identify targets of Alk signaling in the larval CNS. TaDa was employed in larval CNS tissues, while genetically manipulating Alk signaling output. The resulting TaDa data were analysed together with larval CNS scRNA-seq datasets performed under similar conditions, identifying a role for Alk in the transcriptional regulation of neuroendocrine gene expression. Further integration with bulk/scRNA-seq and protein datasets from larval brains in which Alk signaling was manipulated, identified a previously uncharacterized Drosophila neuropeptide precursor encoded by CG4577 as an Alk signaling transcriptional target. CG4577, which we named Sparkly (Spar), is expressed in a subset of Alk-positive neuroendocrine cells in the developing larval CNS, including circadian clock neurons. In agreement with our TaDa analysis, overexpression of the Drosophila Alk ligand Jeb resulted in increased levels of Spar protein in the larval CNS. We show that Spar protein is expressed in circadian (Clock) neurons, and flies lacking Spar exhibit defects in sleep and circadian activity control. In summary, we report a novel activity regulating neuropeptide precursor gene that is regulated by Alk signaling in the Drosophila CNS.

developmental biology↗

bioRxiv2022

Patient-associated mutations in Drosophila Alk perturb neuronal differentiation and promote survival

Activating Anaplastic Lymphoma Kinase (ALK) receptor tyrosine kinase (RTK) mutations occur in pediatric neuroblastoma and are associated with poor prognosis. To study ALK-activating mutations in a genetically controllable system we employed CRIPSR/Cas9, incorporating orthologues of the human oncogenic mutations ALKF1174L and ALKY1278S in the Drosophila Alk locus. AlkF1251L and AlkY1355S mutant Drosophila exhibit enhanced Alk signaling phenotypes, but unexpectedly depend on the Jelly belly (Jeb) ligand for activation. Both AlkF1251L and AlkY1355S mutant larval brains display hyperplasia, represented by increased numbers of Alk-positive neurons. Despite this hyperplasic phenotype, no brain tumors were observed in mutant animals. We show that hyperplasia in Alk mutants was not caused by significantly increased rates of proliferation, but rather by decreased levels of apoptosis in the larval brain. Using single-cell RNA sequencing (scRNA-seq), we identify perturbations during temporal fate specification in AlkY1355S mutant mushroom body lineages. These findings shed light on the role of Alk in neurodevelopmental processes and highlight the potential of activating Alk mutations to perturb specification and promote survival in neuronal lineages.

cancer biology↗

bioRxiv2021

Snail maintains the stem/progenitor state of skin epithelial cells and carcinomas through the autocrine effect of the matricellular protein Mindin

Intratumoral heterogeneity poses a major challenge in designing effective anti-cancer strategies. Accumulating evidence suggests that this heterogeneity arises from cancer stem cells (CSCs) that also drives tumor aggressiveness and drug resistance. The stemness of CSCs are preserved by an ill-defined combination of intrinsic and external factors and is particularly intriguing since they exist within a sea of similar cells at various degrees of differentiation. In models of cutaneous squamous cell carcinoma (cSCC), we discovered a non-EMT function for the transcription factor Snail in maintaining stemness of keratinocytes. This is accomplished by the secretion of the matricellular protein Mindin from Snail expressing cells, which creates a protective niche that impedes differentiation. In an autocrine fashion, extracellular Mindin activates a Src -STAT3 pathway to reinforce the stem/progenitor phenotype and disruption of this signalling module in human cSCC attenuates tumorigenesis. The expression of Mindin in multiple carcinomas, and its critical role in cancer progression suggests that it would be a promising target for therapeutic intervention.

cell biology↗