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Dissection, Culture and Analysis of Primary Cranial Neural Crest Cells from Mouse for the Study of Neural Crest Cell Delamination and Migration
Published on: October 3, 2019
Focal adhesion kinase is required for neural crest cell morphogenesis during mouse cardiovascular development
Ainara Vallejo-Illarramendi1, Keling Zang, Louis F Reichardt
1Department of Physiology, UCSF, San Francisco, California 94158-2611, USA. ainaravallejo@yahoo.es
The Journal of Clinical Investigation
|July 10, 2009
Summary
Focal adhesion kinase (FAK) is crucial for neural crest cell (NCC) development. Deleting FAK in NCCs causes cardiovascular defects, highlighting FAK
Area of Science:
- Cardiovascular Development
- Cell Biology
- Developmental Biology
Background:
- Neural crest cells (NCCs) are vital for cardiovascular development, particularly in remodeling the cardiac outflow tract and pharyngeal arch arteries.
- Focal adhesion kinase (FAK) is a key signaling mediator for integrin and growth factor receptors, essential for cardiovascular development.
Purpose of the Study:
- To investigate the role of FAK in NCC morphogenesis and its contribution to cardiovascular development.
- To understand the molecular mechanisms by which FAK influences NCC differentiation and migration.
Main Methods:
- Deletion of FAK in murine NCCs using Wnt1cre.
- Analysis of craniofacial and cardiovascular malformations in knockout mice.
- Assessment of NCC differentiation, migration, and mesenchymal organization in vivo and in vitro.
- Examination of signaling pathways, including Crkl and Erk1/2 phosphorylation.
Main Results:
- FAK deletion in NCCs led to cardiovascular malformations resembling DiGeorge syndrome.
- Observed impaired cardiac outflow tract rotation and reduced smooth muscle differentiation in aortic arch arteries.
- Fak-deficient NCCs showed disorganized mesenchyme, reduced perlecan and semaphorin 3C expression, and disrupted F-actin.
- Absence of FAK resulted in reduced in vivo phosphorylation of Crkl and Erk1/2.
Conclusions:
- FAK is essential for cardiac outflow tract development in NCCs.
- FAK promotes NCC differentiation and mesenchymal organization through signaling pathways involving Crkl and Erk1/2.
- FAK deficiency leads to specific cardiovascular defects, underscoring its critical role.
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