Axon Guidance Molecules in the Islets of Langerhans

Waters, Bayley J.; Blum, Barak

doi:10.3389/fendo.2022.869780

Cited by 7 publications

(5 citation statements)

References 52 publications

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“…Interestingly, several of these genes including Kit, Slit1, Sdc3, Map1b, Dab1, Olfm1, Dpysl5 and Flrt1 are involved in morphogenetic processes (Figure 5G). Among them, Slit1 belongs to Slit family of secreted extracellular matrix proteins, which have been recently reported to regulate endocrine cell morphogenesis during mouse endocrinogenesis (34,35). Therefore, this analysis predicts a possible function of Neurod2 in regulating programs that coordinate endocrine cell morphogenesis.…”

Section: Resultsmentioning

confidence: 87%

NEUROD2 function is dispensable for human pancreatic β cell specification

Cota,

Saber,

Taskin

et al. 2023

Front. Endocrinol.

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IntroductionThe molecular programs regulating human pancreatic endocrine cell induction and fate allocation are not well deciphered. Here, we investigated the spatiotemporal expression pattern and the function of the neurogenic differentiation factor 2 (NEUROD2) during human endocrinogenesis.MethodsUsing Crispr-Cas9 gene editing, we generated a reporter knock-in transcription factor (TF) knock-out human inducible pluripotent stem cell (iPSC) line in which the open reading frame of both NEUROD2 alleles are replaced by a nuclear histone 2B-Venus reporter (NEUROD2nVenus/nVenus).ResultsWe identified a transient expression of NEUROD2 mRNA and its nuclear Venus reporter activity at the stage of human endocrine progenitor formation in an iPSC differentiation model. This expression profile is similar to what was previously reported in mice, uncovering an evolutionarily conserved gene expression pattern of NEUROD2 during endocrinogenesis. In vitro differentiation of the generated homozygous NEUROD2nVenus/nVenus iPSC line towards human endocrine lineages uncovered no significant impact upon the loss of NEUROD2 on endocrine cell induction. Moreover, analysis of endocrine cell specification revealed no striking changes in the generation of insulin-producing b cells and glucagon-secreting a cells upon lack of NEUROD2.DiscussionOverall, our results suggest that NEUROD2 is expendable for human b cell formation in vitro.

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Section: Resultsmentioning

confidence: 87%

NEUROD2 function is dispensable for human pancreatic β cell specification

Cota,

Saber,

Taskin

et al. 2023

Front. Endocrinol.

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“…For example, recent molecular data obtained from the mouse pancreas showed that epithelial islet cells express Robo receptors. Inactivating Slit-Robo signaling disrupted embryonic islet formation and adult islet architecture 66, 67 , emphasizing an underappreciated role for axon guidance molecules in extra-neuronal contexts. In Drosophila, Robo2 was suggested to be induced by high cell-autonomous JNK signaling and required for the elimination of scrib mutant cells 45 .…”

Section: Discussionmentioning

confidence: 99%

A cell surface code mediates tissue-intrinsic defense against aberrant cells in epithelia

Fischer

Ernst

Frey

et al. 2023

Preprint

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Tissue-intrinsic error-correction mechanisms allow epithelial cells to detect aberrant neighboring cells and cause their removal from the tissue. The molecular mechanisms which grant cells the ability to compare their internal states is unknown. Here we demonstrate that comparison of cell identity, created by cell-fate-specifying transcription factors and patterning pathways, is conveyed through a specific set of cell surface molecules. We demonstrate thatDrosophilaimaginal discs express a range of cell surface molecules previously implicated in neuronal axon guidance processes, such as members of the Robo, Teneurin, Ephrin, Toll-like or atypical Cadherin families. Expression of these molecules is regulated by intrinsic fate-patterning pathways of the disc but also by aberrant expression of oncogenic RasV12. Importantly, mosaic clones deregulating individual cell surface molecules are sufficient to induce all hallmarks of interface surveillance, a tissue-intrinsic error-correction mechanism previously shown to be induced by cells with aberrant activation of fate-patterning pathways. Specifically, cells with deregulated expression of Robo2 and Robo3 induce actomyosin enrichment, bilateral JNK signaling and apoptosis at mosaic clone interfaces in imaginal discs. Moreover, deregulation of Robo2 levels, which is normally expressed in a complex endogenous pattern, induces these interface surveillance hallmarks in a Robo2-pattern-specific manner. Taken together, our work indicates that these cell surface molecules mediate cell fate recognition in epithelial tissues and thereby contribute to the maintenance of epithelial health by initiating detection and removal of aberrant cells during development and adult tissue homeostasis.

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“…Axon guidance plays a vital role in neuronal development and regeneration, regulating the cytoskeleton of growth cones and promoting growth cones to advance, pause, turn, or collapse [40]. In addition, axon guidance affects islet morphology and function by regulating the migration of endocrine progenitor cells, which impacts the level of blood glucose metabolism in the body [41]. Axon guidance molecules interact with receptors to affect the development, maintenance, and resolution of tumors and neuropathic pain through Wnt2 signaling, Eph-ephrin signaling, and the semaphorin-plexin system [42].…”

Section: Discussionmentioning

confidence: 99%

Screening Differential Expression Profiles of Urinary microRNAs in a Gentamycin-Induced Acute Kidney Injury Canine Model

Sun

Chen

et al. 2023

Kidney and Dialysis

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microRNAs (miRNAs) are promising biomarkers for different pathological models because of their stable and detectable characters in biofluids. Here, we collected urine samples from 5 beagle dogs on the 3th, 6th, and 12th day in an acute kidney injury (AKI) caused by gentamycin. miRNA levels were measured with high-throughput sequencing and the results were then differentially investigated. Gene Ontology (GO) and KEGG pathway analysis were performed to analyze potential target genes corresponding to the differentially expressed miRNAs (DE-miRNAs). Relationships between hub genes and DE-miRNAs were analyzed with STRING and Cytoscape. We identified 234 DE-miRNAs 3, 6, and 12 days after gentamycin treatment (p < 0.05). Top 10 up- and down-regulated candidate target genes of DE-miRNAs were predicted by overlapping TargetScan and miRanda results). GO and KEGG analyses for DE-miRNAs demonstrated that the DE-miRNAs target genes are mainly involved in kidney injury-related pathways, such as the insulin signaling pathway, oxytocin signaling pathway, and hedgehog signaling pathway. The network of miRNA-hub genes suggests that miR-452, miR-106a, and 106b participate in regulating the largest number of hub genes. We evaluated the miRNA signature via a canine model built by gentamycin-caused acute kidney injury. Our results represent a valuable resource for evaluating miRNAs as biomarkers of renal toxicity.

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Axon Guidance Molecules in the Islets of Langerhans

Cited by 7 publications

References 52 publications

NEUROD2 function is dispensable for human pancreatic β cell specification

NEUROD2 function is dispensable for human pancreatic β cell specification

A cell surface code mediates tissue-intrinsic defense against aberrant cells in epithelia

Screening Differential Expression Profiles of Urinary microRNAs in a Gentamycin-Induced Acute Kidney Injury Canine Model

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