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Open research questions in Connexins and lens biology

150 gap statements mined from Connexins and lens biology papers in our 7.9M-paper local library, which holds 424 papers on the topic — drawn mostly from each paper's own stated research gap, future-work, challenge and limitation notes, and its abstract. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one.

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What the literature leaves open

  • One challenge is the low yield of observing cell pairs with functional gap junctions, particularly for Cx45. Another challenge is the potential for voltage clamp errors, which was addressed by selecting cell pairs with gap junction coupling conductance values between 3 and 9 nS.

    Hydrogen peroxide reduces Cx40, Cx43, and Cx45 gap junction function · 2026 · DOI

  • Further investigations to delineate the contributions of gap junctional versus non-junctional Cx43 pools and to map compensatory signaling pathways that may influence responses to dual kinase inhibition.

    Disrupting oncogenic signaling in triple negative breast cancer: The interplay of Cx43, Pyk2, and Src in MDA-MB-231 cells · 2026 · DOI

  • The interplay between Cx43, Pyk2, and Src is not well understood in the context of triple negative breast cancer. The study aims to address this gap by investigating the role of Cx43, Pyk2, and Src in MDA-MB-231 cells. The lack of understanding of the signaling pathways involved in triple negative breast cancer is a significant research gap.

    Disrupting oncogenic signaling in triple negative breast cancer: The interplay of Cx43, Pyk2, and Src in MDA-MB-231 cells · 2026 · DOI

  • A gap in understanding remains, particularly in how connexins, pannexins, and innexins create elaborate communication networks. The properties of individual channels and how they scale to produce tissue-level behavior are not well understood.

    From channels to communication networks: a perspective on connexins, pannexins and innexins · 2026 · DOI

  • Understanding the underlying mechanisms of dentin hypersensitivity is a significant challenge. Developing effective treatments for dentin-associated diseases and dentin-pulp regeneration is a major challenge. The lack of emphasis on dental research has hindered progress in understanding dentin mechanobiology.

    Dentin Mechanobiology: Bridging the Gap between Architecture and Function · 2024 · DOI

  • The spatial heterogeneity of astrocyte density, morphology, and connexin expression in the hippocampus is not well understood. There is a lack of comprehensive analysis of astrocyte distribution in the hippocampus.

    Heterogeneity of astrocyte density, morphology and connexins in the mouse hippocampus · 2026 · DOI

  • However, which AP-1 members more strongly activate Cx43 expression, and the signaling pathways involved, remain to be confirmed.

    The AP-1 transcription factors differentially regulate Cx43 expression in a ERK1/2-dependent manner in MA-10 Leydig cells · 2026 · DOI

  • However, direct evidence of the involvement of these Cxs in the reactivation of the ependymal stem cell niche is lacking.

    Connexins are essential for the contribution of latent progenitors to healing after spinal cord injury · 2026 · DOI

  • The effects of itaconate on connexin expression in neural stem cells are unclear. The potential of itaconate to modulate neural stem cell fate and differentiation is not well understood. The interaction network between connexins and itaconate-mediated signaling has not been fully elucidated.

    Connexin Regulation and Modulation of Neural Stem Cell Differentiation Induced by Cell‐Permeable Itaconate · 2026 · DOI

  • RORα is decreased in the lens from patients with cataract, but it remains unclear whether decreases in RORα are attributed to cataract formation.

    Targeting Retinoic Acid Receptor-Related Orphan Receptor α to Prevent Cataracts: A New Pathway Through Nerve Growth Factor Activation · 2026 · DOI

  • While many cataract-causing missense and nonsense mutations are known for these genes, including the human CRYBB3 gene, the mammalian loss-of function model of Crybb3 remains to be established.

    Analysis of mouse lens morphological and proteomic abnormalities following deletion of the βB3-crystallin promoter · 2025 · DOI

  • However, its functions within the central nervous system (CNS) are not fully understood.

    Connexin 43 Role in Mitochondrial Transfer and Homeostasis in the Central Nervous System · 2025 · DOI

  • Although the underlying molecular pathways remain to be identified, we observed a remarkable overproduction of C1qtnf3, especially in neonatal Panx3-deficient animals.

    Panx3 deficiency in mice impairs bone fracture healing and causes transient hypoglycemia in neonatal animals · 2026 · DOI

  • The need to identify therapeutic targets for accelerating hematologic recovery after cytotoxic injury.

    Bone marrow stem cell connexins: misconceptions and new insights · 2026 · DOI

  • Given the emerging evidence linking variant localization within Cx43 to phenotypic expression, genotype–phenotype studies are warranted to better define the full spectrum of ocular involvement in ODDD.

    Megalopapilla in oculodentodigital dysplasia: a novel ocular finding in a rare genetic disorder · 2026 · DOI

  • Cataract remains a leading cause of treatable blindness worldwide. The precise mechanism of cataractogenesis is not fully understood. Metabolic disturbances, including electrolyte imbalances, may contribute to cataract development.

    Comparison of serum sodium and potassium levels in patients with cataract and individuals without cataract in a tertiary care center in North Kerala: a cross-sectional study · 2026 · DOI

  • The study is limited to individuals aged 50-60 years. The study does not investigate the effect of age-related decline in Na⁺/K⁺-ATPase pump activity on electrolyte homeostasis.

    Comparison of serum sodium and potassium levels in patients with cataract and individuals without cataract in a tertiary care center in North Kerala: a cross-sectional study · 2026 · DOI

  • Although signaling and metabolic pathways regulate NMP states, whether intercellular communication contributes to the coordination of progenitor behaviour and developmental timing remains unclear.

    Connexin-43 links Neuromesodermal progenitor states to segmentation clock robustness during vertebrate axis elongation · 2026 · DOI

  • Consistent with these findings, pairwise EL2 motif similarity was only modestly associated with threshold-based interaction classification, indicating that EL2 similarity alone was insufficient to predict compatibility outcomes.

    A family-wide atlas of human connexin docking compatibility · 2026 · DOI

  • The complexity of the maternal-fetal interface and the need for a comprehensive understanding of large-pore channel expression and function. The lack of experimental evidence for Panx1-mediated ATP release specifically in primary human trophoblasts. The need for larger prospective studies to determine the causal relationship between Cx43 downregulation and recurrent pregnancy loss.

    Large-Pore Channels at the Maternal–Fetal Interface: Progress and Open Research Avenues · 2026 · DOI

  • The need for protein-level validation of CALHM and LRRC8 expression in primary trophoblasts. The lack of understanding of gating mechanisms and crosstalk among channel families. The need for elucidation of the functional role of Panx1 or Cx43 in immune cells at the maternal-fetal interface.

    Large-Pore Channels at the Maternal–Fetal Interface: Progress and Open Research Avenues · 2026 · DOI

  • Spatially resolved transcriptomics and proteomics are starting to map the architecture of these communication networks in intact tissues - Computational modelling is helping to generate testable ideas about how network structure and channel properties work together to produce collective…

    From channels to communication networks: a perspective on connexins, pannexins and innexins · 2026 · DOI

  • Using complementary approaches and genetic evidence, including Cx36 knockdown or knockout strategies, to further clarify the contribution of this Cx to the observed effects of DMI on NSCs differentiation profile - Investigating the ability of cell-permeable itaconate derivatives to modulate Cxs expression patterns and impact on cell fate - Studying the role of Cx43 in modulating proliferation and neurogenesis…

    Connexin Regulation and Modulation of Neural Stem Cell Differentiation Induced by Cell‐Permeable Itaconate · 2026 · DOI

  • The accumulated number of research articles on dentin mechanobiology remains relatively small, - There are no effective treatments for dentin hypersensitivity because the underlying mechanisms are not well understood, - Dental diseases are not fatal, which has led to a lack of emphasis on dental…

    Dentin Mechanobiology: Bridging the Gap between Architecture and Function · 2024 · DOI

  • Investigating the therapeutic potential of boosting connexins to accelerate hematologic recovery. Exploring the role of connexins in other diseases, such as leukemia and myelodysplastic syndromes.

    Bone marrow stem cell connexins: misconceptions and new insights · 2026 · DOI

Most-cited papers in Connexins and lens biology

Most recent work

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Open questions raised by papers listed on this page include: (1) The interplay between Cx43, Pyk2, and Src is not well understood in the context of triple negative breast cancer (“Disrupting oncogenic signaling in triple negative breast cancer: The interplay…”, 2026); (2) The properties of individual channels and how they scale to produce tissue-level behavior are not well understood (“From channels to communication networks: a perspective on connexins, pannexins…”, 2026); (3) The spatial heterogeneity of astrocyte density, morphology, and connexin expression in the hippocampus is not well understood (“Heterogeneity of astrocyte density, morphology and connexins in the mouse…”, 2026); (4) Which AP-1 members more strongly activate Cx43 expression, and the signaling pathways involved, remain to be confirmed (“The AP-1 transcription factors differentially regulate Cx43 expression in a…”, 2026); (5) Direct evidence of the involvement of these Cxs in the reactivation of the ependymal stem cell niche is lacking (“Connexins are essential for the contribution of latent progenitors to healing…”, 2026). 150 gap statements have been mined from Connexins and lens biology papers in our 7.9M-paper local library, which holds 424 papers on the topic; the gaps come from whichever of those papers state one. They are mostly the research gaps the authors state and the papers' abstracts, plus future-work, limitations and challenges passages. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one, so you can read the original claim in context.

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