Calponin 2 Acts As an Effector of Noncanonical Wnt-Mediated Cell Polarization during Neural Crest Cell Migration

• Published in: Cell reports (Cambridge) Vol. 3; no. 3; pp. 615 - 621
• Main Authors: Ulmer, Bärbel, Hagenlocher, Cathrin, Schmalholz, Silke, Kurz, Sabrina, Schweickert, Axel, Kohl, Ayelet, Roth, Lee, Sela-Donenfeld, Dalit, Blum, Martin
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 28.03.2013; Elsevier
• Subjects: Actins - metabolism; Amino Acid Sequence; Animals; Anura; Calcium-Binding Proteins - genetics; Calcium-Binding Proteins - metabolism; Calponins; Cell Movement; Cell Surface Extensions - metabolism; Chick Embryo; Embryo, Nonmammalian - cytology; Embryo, Nonmammalian - metabolism; Embryonic Stem Cells - metabolism; Embryonic Stem Cells - physiology; In Vitro Techniques; Microfilament Proteins - genetics; Microfilament Proteins - metabolism; Molecular Sequence Data; Neural Crest - cytology; Neural Crest - metabolism; rhoA GTP-Binding Protein - metabolism; Wnt Proteins - metabolism; Wnt Signaling Pathway; Xenopus
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2013.02.015

Neural crest cells (NCCs) migrate throughout the embryo to differentiate into cell types of all germ layers. Initial directed NCC emigration relies on planar cell polarity (PCP), which through the activity of the small GTPases RhoA and Rac governs the actin-driven formation of polarized cell protrusions. We found that the actin binding protein calponin 2 (Cnn2) was expressed in protrusions at the leading edge of migratory NCCs in chicks and frogs. Cnn2 knockdown resulted in NCC migration defects in frogs and chicks and randomized outgrowth of cell protrusions in NCC explants. Morphant cells showed central stress fibers at the expense of the peripheral actin network. Cnn2 acted downstream of Wnt/PCP, as migration defects induced by dominant-negative Wnt11 or inhibition of RhoA function were rescued by Cnn2 knockdown. These results suggest that Cnn2 modulates actin dynamics during NCC migration as an effector of noncanonical Wnt/PCP signaling. [Display omitted] ► Cnn2 is expressed in NCCs and required for their migration in frogs and chicks ► Cnn2 is inactivated by noncanonical Wnt signaling ► Loss of Cnn2 causes a switch from cortical actin to central stress fibers ► Cnn2 polarizes the actin cytoskeleton downstream of PCP Neural crest cells (NCCs) delaminate and migrate through filopodia and lamellipodia. Protrusions form in a Wnt/planar cell polarity (PCP)-dependent manner where cells have no contact to direct them away from the closing neural tube. Sela-Donenfeld, Blum, and colleagues show that the actin binding protein calponin 2 (Cnn2) is required for NCC migration in frogs and chicks, and that Cnn2 acts downstream of Wnt/PCP to polarize the actin cytoskeleton at the leading edge of migratory NCCs.