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The primary cilium, made up of microtubules, acts as antennae on the cell surfaces for relaying external stimuli into the cells. These fine hair-like structures are present, generally one per cell. These are non-motile cilia in a 9+0 microtubules arrangement, where the central pair of microtubules are absent. The primary cilia arise from the basal body embedded in the cell membrane. Intraflagellar transport (IFT) carries requisite proteins from the cytoplasm to the cilium because the primary...
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Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
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Filopodia are thin, actin-rich cellular protrusions that play an important role in many fundamental cellular functions. They vary in their occurrence, length, and positioning in different cell types, suggesting their diverse roles.
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Cell polarity is the asymmetric distribution of cellular and membrane components, making one side of the cell different from the other. This polarity is essential to many processes such as embryogenesis, axon migration, glucose transport across epithelial cells, and directional cell migration. A migrating cell responds to intracellular or extracellular signals via molecular cascades that reorganize the actin cytoskeleton to establish this polarity. In these cells, the Rho family proteins Cdc42,...
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The ciliary structures were first seen in 1647 by Antonie Leeuwenhoek while observing the protozoans. In lower organisms, these appendages are responsible for cell movement, while in higher organisms, these appendages help in the movement of the extracellular fluids within the body cavities.
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The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
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Related Experiment Video

Updated: Sep 19, 2025

Using Primary Neurosphere Cultures to Study Primary Cilia
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The primary cilium as a gatekeeper of FGFR2 function.

Raman Kaushik1, Raj K Ladher1

  • 1National Centre for Biological Sciences, NCBS-TIFR , Bangalore, India.

The Journal of Cell Biology
|June 18, 2025
PubMed
Summary

The primary cilium acts as a gatekeeper, controlling Fibroblast Growth Factor Receptor 2 (FGFR2) signaling. Spatial organization within the cilium ensures selective activation, crucial for development and disease.

Area of Science:

  • Cell Biology
  • Molecular Signaling
  • Developmental Biology

Background:

  • The primary cilium is a critical cellular organelle involved in various signaling pathways.
  • Fibroblast Growth Factor Receptor 2 (FGFR2) signaling plays a vital role in embryonic development and is implicated in various diseases.
  • Dysregulation of FGFR2 signaling is linked to developmental abnormalities and certain cancers.

Purpose of the Study:

  • To investigate the role of the primary cilium in regulating FGFR2 signaling.
  • To understand how spatial compartmentalization within the cilium affects downstream signaling events.
  • To examine the impact of disease-linked FGFR2 variants on ciliary localization and signaling.

Main Methods:

  • Utilized advanced microscopy techniques to visualize FGFR2 localization within primary cilia.

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  • Employed biochemical assays to assess downstream signaling pathway activation.
  • Generated and analyzed cell models expressing disease-associated FGFR2 variants.

    • Main Results:

    • Demonstrated that the primary cilium spatially compartmentalizes FGFR2 signaling components.
    • Showed that this compartmentalization enables selective activation of downstream effectors.
    • Observed that disruption of ciliary localization of FGFR2 variants impairs normal signaling.

    Conclusions:

    • The primary cilium functions as a critical signaling gatekeeper for FGFR2.
    • Spatial organization within the cilium is essential for precise control of FGFR2-mediated developmental processes.
    • Ciliary dysfunction in FGFR2 signaling contributes to developmental disorders and disease pathogenesis.