Coordination by Cdc42 of Actin, Contractility, and Adhesion for Melanoblast Movement in Mouse Skin

Emma F Woodham1, Nikki R Paul1, Benjamin Tyrrell1

  • 1CRUK Beatson Institute, University of Glasgow, Switchback Road, Bearsden, Glasgow G61 1BD, UK.

Current Biology : CB
|February 28, 2017
PubMed

Insights

Cellular migration relies on coordinated pathways. Cdc42 (cell division control protein 42) is crucial for melanoblast movement, independent of Rac1, by organizing actin assembly, myosin localization, and cell adhesion.

Area of Science:

  • Cell Biology
  • Developmental Biology
  • Molecular Biology

Background:

  • Cell migration is vital for embryonic development, particularly for neural crest-derived melanoblasts reaching their epidermal targets.
  • While Rac GTPases' roles in cell motility are known, their coordination with other GTPases in complex in vivo environments remains unclear.
  • Previous work identified Rac1 signaling through Scar/WAVE and Arp2/3 for melanoblast pseudopod extension and migration.

Purpose of the Study:

  • To investigate the role of Cdc42 in coordinating cellular motility systems during melanoblast migration in vivo.
  • To determine if Cdc42 acts independently of Rac1 in regulating melanoblast migration and other cellular processes.

Main Methods:

  • Analysis of Cdc42 null mice and melanoblasts.
  • Assessment of melanoblast cell-cycle progression, migration, and cytokinesis.
  • Microscopic examination of cell morphology, pseudopod dynamics, and actin polymerization.
  • Evaluation of Golgi polarization and coordination of motility systems.

Main Results:

  • Cdc42 is essential for melanoblast migration, with Cdc42 null mice showing severe pigmentation loss and developmental defects.
  • Cdc42 null melanoblasts exhibit elongated shapes and bulky pseudopods but migrate slowly and inefficiently.
  • Loss of Cdc42 disrupts the coordination of actin assembly (FMNL2/Arp2/3), myosin-II localization, and integrin adhesion dynamics.
  • Cdc42 null cells fail to polarize their Golgi, indicating a breakdown in directed cell movement.

Conclusions:

  • Cdc42 plays a critical, Rac1-independent role in coordinating multiple cellular motility systems essential for melanoblast migration.
  • Cdc42 is required for proper Golgi polarization and the integration of actin dynamics, myosin activity, and cell adhesion.
  • Disruption of Cdc42 function leads to severe defects in cell migration and development, highlighting its importance in complex cellular behaviors.

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