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The planar cell polarity pathway and parietal endoderm cell migration
Kristi Lamonica1, Laura Grabel
1Department of Craniofacial Biology, School of Dental Medicine, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO, USA.
Insights
Parietal endoderm cell migration relies on the Planar Cell Polarity (PCP) pathway. Wnt inhibition disrupts cell orientation and migration, highlighting non-canonical Wnt/PCP signaling
Area of Science:
- Developmental biology
- Cell biology
- Embryogenesis
Background:
- Parietal endoderm (PE) cell migration is crucial for mammalian embryonic development, forming the parietal yolk sac.
- The F9 teratocarcinoma stem cell model system provides an in vitro platform to study PE migration dynamics.
Purpose of the Study:
- To investigate the molecular mechanisms directing parietal endoderm cell migration.
- To elucidate the role of the Planar Cell Polarity (PCP) pathway and Rho/ROCK signaling in PE orientation.
Main Methods:
- Utilized the F9 teratocarcinoma stem cell model for in vitro studies.
- Manipulated Wnt signaling using sFRP and assessed cell migration and orientation.
- Analyzed Golgi apparatus localization, microtubule organization, and focal adhesions.
- Investigated the involvement of small GTPases (Rho/ROCK, Rac) in PCP signaling.
Main Results:
- Wnt inhibition via sFRP led to a loss of migratory orientation and disorganized cellular structures.
- Rho/ROCK pathway inhibition resulted in impaired cell orientation, while Rac inhibition had no significant effect.
- Non-canonical Wnt/PCP signaling was identified as a key regulator of oriented PE migration.
Conclusions:
- Non-canonical Wnt/PCP signaling, mediated by Rho/ROCK, is essential for directing parietal endoderm cell migration.
- Disruption of this pathway leads to loss of cell polarity and disorganized migration patterns.
- Findings provide insights into the fundamental processes governing early embryonic cell movements.
Abstract:
Parietal endoderm (PE) migration is the first long-range migratory event in the mammalian embryo contributing to the parietal yolk sac. PE migration can be studied in vitro using the F9 teratocarcinoma stem cell model system. We have found that PE migration is directed and modulated via the Planar Cell Polarity (PCP) pathway through Rho/ROCK signaling. Wnt inhibition using sFRP results in a loss of orientation, visualized by Golgi apparatus localization, along with disorganized microtubules and a lack of robust focal adhesions. Small GTPases are downstream of PCP signaling and Rho/ROCK inhibition results in a loss of orientation, whereas inhibition of Rac does not affect PCP. Activation of canonical Wnt signaling combined with Wnt inhibition does not prevent loss of oriented migration. These data support a role for non-canonical Wnt/PCP signaling directing oriented migration of PE.
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