Cell intrinsic modulation of Wnt signaling controls neuroblast migration in C. elegans.
Members of the Wnt family of secreted signaling proteins are key regulators of cell migration and axon guidance. In the nematode C. elegans, the migration of the QR neuroblast descendants requires multiple Wnt ligands and receptors. We found that the migration of the QR descendants is divided into three sequential phases that are each mediated by a distinct Wnt signaling mechanism. Importantly, the transition from the first to the second phase, which is the main determinant of the final position of the QR descendants along the anteroposterior body axis, is mediated through a cell-autonomous process in which the time-dependent expression of a Wnt receptor turns on the canonical Wnt/β-catenin signaling response that is required to terminate long-range anterior migration. Our results show that, in addition to direct guidance of cell migration by Wnt morphogenic gradients, cell migration can also be controlled indirectly through cell-intrinsic modulation of Wnt signaling responses.
Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences and University Medical Center Utrecht, Uppsalalaan 8, 3584 CT Utrecht, the Netherlands.
Remco A
RA
Mentink
Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences and University Medical Center Utrecht, Uppsalalaan 8, 3584 CT Utrecht, the Netherlands.
Teije C
TC
Middelkoop
Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences and University Medical Center Utrecht, Uppsalalaan 8, 3584 CT Utrecht, the Netherlands.
Lorenzo
L
Rella
Department of Physics and Department of Biology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA; Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
Ni
N
Ji
Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences and University Medical Center Utrecht, Uppsalalaan 8, 3584 CT Utrecht, the Netherlands.
Chung Yin
CY
Tang
Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences and University Medical Center Utrecht, Uppsalalaan 8, 3584 CT Utrecht, the Netherlands.
Marco C
MC
Betist
Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences and University Medical Center Utrecht, Uppsalalaan 8, 3584 CT Utrecht, the Netherlands; Department of Physics and Department of Biology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
Alexander
A
van Oudenaarden
Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences and University Medical Center Utrecht, Uppsalalaan 8, 3584 CT Utrecht, the Netherlands. Electronic address: r.korswagen@hubrecht.eu.
Hendrik C
HC
Korswagen
D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology / Q000254:growth & development*; D029742:Caenorhabditis elegans Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D002465:Cell Movement / Q000235:genetics*; D016764:Cell Polarity; D051157:Frizzled Receptors / Q000096:biosynthesis / Q000378:metabolism; D005786:Gene Expression Regulation / Q000235:genetics; D006023:Glycoproteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D009024:Morphogenesis; D058953:Neural Stem Cells / Q000166:cytology / Q000502:physiology*; D010750:Phosphoproteins / Q000378:metabolism; D057050:Receptor Tyrosine Kinase-like Orphan Receptors / Q000235:genetics / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000096:biosynthesis; D014157:Transcription Factors / Q000235:genetics; D051153:Wnt Proteins / Q000096:biosynthesis / Q000378:metabolism*; D060449:Wnt Signaling Pathway / Q000235:genetics*; D051176:beta Catenin / Q000378:metabolism
C109217:CEH-22 protein, C elegans; C526268:CWN-1 protein, C elegans; D029742:Caenorhabditis elegans Proteins; C117259:Egl-20 protein, C elegans; D051157:Frizzled Receptors; D006023:Glycoproteins; D018398:Homeodomain Proteins; D047908:Intracellular Signaling Peptides and Proteins; C101684:LIN-17 protein, C elegans; D008565:Membrane Proteins; C554442:Mig-1 protein, C elegans; C108315:Mom-5 protein, C elegans; C569184:PRKL-1 protein, C elegans; D010750:Phosphoproteins; D043562:Receptors, G-Protein-Coupled; D014157:Transcription Factors; C549532:Vang-1 protein, C elegans; D051153:Wnt Proteins; D051176:beta Catenin; C526267:CAM-1 protein, C elegans; D057050:Receptor Tyrosine Kinase-like Orphan Receptors