A Src-Tks5 pathway is required for neural crest cell migration during embryonic development

Danielle A. Murphy, Begoña Diaz, Paul A. Bromann, Jeff H. Tsai, Yasuhiko Kawakami, Jochen Maurer, Rodney A. Stewart, Juan Carlos Izpisúa-Belmonte, Sara Courtneidge

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

In the adult organism, cell migration is required for physiological processes such as angiogenesis and immune surveillance, as well as pathological events such as tumor metastasis. The adaptor protein and Src substrate Tks5 is necessary for cancer cell migration through extracellular matrix in vitro and tumorigenicity in vivo. However, a role for Tks5 during embryonic development, where cell migration is essential, has not been examined. We used morpholinos to reduce Tks5 expression in zebrafish embryos, and observed developmental defects, most prominently in neural crest-derived tissues such as craniofacial structures and pigmentation. The Tks5 morphant phenotype was rescued by expression of mammalian Tks5, but not by a variant of Tks5 in which the Src phosphorylation sites have been mutated. We further evaluated the role of Tks5 in neural crest cells and neural crest-derived tissues and found that loss of Tks5 impaired their ventral migration. Inhibition of Src family kinases also led to abnormal ventral patterning of neural crest cells and their derivatives. We confirmed that these effects were likely to be cell autonomous by shRNA-mediated knockdown of Tks5 in a murine neural crest stem cell line. Tks5 was required for neural crest cell migration in vitro, and both Src and Tks5 were required for the formation of actin-rich structures with similarity to podosomes. Additionally, we observed that neural crest cells formed Src-Tks5-dependent cell protrusions in 3-D culture conditions and in vivo. These results reveal an important and novel role for the Src-Tks5 pathway in neural crest cell migration during embryonic development. Furthermore, our data suggests that this pathway regulates neural crest cell migration through the generation of actin-rich pro-migratory structures, implying that similar mechanisms are used to control cell migration during embryogenesis and cancer metastasis.

Original languageEnglish (US)
Article numbere22499
JournalPLoS One
Volume6
Issue number7
DOIs
StatePublished - 2011
Externally publishedYes

Fingerprint

neural crest
Neural Crest
cell movement
Embryonic Development
Cell Movement
Actins
embryogenesis
Tissue
Morpholinos
Phosphorylation
src-Family Kinases
Stem cells
Small Interfering RNA
Tumors
Cells
Derivatives
Defects
Substrates
metastasis
Proteins

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

A Src-Tks5 pathway is required for neural crest cell migration during embryonic development. / Murphy, Danielle A.; Diaz, Begoña; Bromann, Paul A.; Tsai, Jeff H.; Kawakami, Yasuhiko; Maurer, Jochen; Stewart, Rodney A.; Izpisúa-Belmonte, Juan Carlos; Courtneidge, Sara.

In: PLoS One, Vol. 6, No. 7, e22499, 2011.

Research output: Contribution to journalArticle

Murphy, DA, Diaz, B, Bromann, PA, Tsai, JH, Kawakami, Y, Maurer, J, Stewart, RA, Izpisúa-Belmonte, JC & Courtneidge, S 2011, 'A Src-Tks5 pathway is required for neural crest cell migration during embryonic development', PLoS One, vol. 6, no. 7, e22499. https://doi.org/10.1371/journal.pone.0022499
Murphy, Danielle A. ; Diaz, Begoña ; Bromann, Paul A. ; Tsai, Jeff H. ; Kawakami, Yasuhiko ; Maurer, Jochen ; Stewart, Rodney A. ; Izpisúa-Belmonte, Juan Carlos ; Courtneidge, Sara. / A Src-Tks5 pathway is required for neural crest cell migration during embryonic development. In: PLoS One. 2011 ; Vol. 6, No. 7.
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