Related Experiment Video
Updated: Jun 13, 2025
07:26
Quantitative PCR-based Assay to Measure Sonic Hedgehog Signaling in Cellular Model of Ciliogenesis
Published on: January 31, 2025
469
Merlin controls limb development and thumb formation by regulating primary cilium-hedgehog signaling
Shali Wu1, Yan Bian1, Cui Zhang2
1Department of Cell and Developmental Biology, College of Life Sciences, Zhejiang University, Hangzhou, Zhejiang 310000, China.
Cell Reports
|June 12, 2025
Summary
Merlin protein is essential for limb development and thumb formation by regulating Hedgehog (HH) signaling. Enhancing HH signaling can correct limb defects caused by Merlin deficiency.
Area of Science:
- Developmental Biology
- Molecular Biology
- Genetics
Background:
- Hedgehog (HH) signaling is vital for limb development, primarily through primary cilia.
- The role of HH signaling in thumb development is not fully understood.
- Merlin (Nf2) function in limb development requires further elucidation.
Purpose of the Study:
- To investigate the role of Merlin (Nf2) in limb development and thumb morphogenesis.
- To determine Merlin's mechanism in regulating Hedgehog signaling.
- To explore therapeutic potential for Merlin-deficiency-related limb defects.
Main Methods:
- Conditional knockout of Merlin in mouse limb mesenchyme.
- Transcriptomic profiling and molecular analyses.
- Investigation of Merlin's interaction with ARF6 and RAB11 vesicles in Smoothened trafficking.
Main Results:
- Merlin knockout mice exhibited dwarfism, brachydactyly, and thumb hypoplasia.
- Disrupted HH signaling and Smoothened ciliary transport were observed in Merlin-deficient limbs.
- Merlin regulates Smoothened trafficking via ARF6 and RAB11+ vesicles.
- Pharmacological enhancement of HH signaling rescued limb defects.
Conclusions:
- Merlin is a critical regulator of longitudinal limb growth and thumb development.
- Merlin controls limb development by modulating primary cilium-HH signaling.
- Targeting HH signaling may offer therapeutic strategies for limb dysplasias associated with Merlin.
Keywords:
CP: Developmental biologyMerlinSmootheneddigit patterninghedgehoglimb developmentprimary ciliumskeleton developmentthumb hypoplasiaMore Related Videos
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