XPak3 promotes cell cycle withdrawal during primary neurogenesis in Xenopus laevis.
We have isolated the Xenopus p21-activated kinase 3 (XPak3) by virtue of its expression in the territory of primary neurogenesis in the developing embryo. XPak3, but not the other Pak variants, responds positively to X-Ngnr-1 and negatively to X-Notch-1. A constitutively active form of XPak3, generated by fusing a myristylation signal to the N-terminus (XPak3-myr), induces early cell cycle arrest at high concentrations, while ectopic expression of low amounts induces premature neuronal differentiation. Conversely, XPak3 loss of function achieved by use of an antisense morpholino oligonucleotide increases cell proliferation and inhibits neuronal differentiation; this phenotype is rescued by co-injection of XPak3-myr. We conclude that XPak3 is a novel member of the proneural pathway, functioning downstream of neurogenin to withdraw neuronally programmed cells from the mitotic cell cycle, thus allowing for their differentiation.
Souopgui
Jacob
J
Institut für Biochemie und Molekulare Zellbiologie, Georg-August-Universität Göttingen, Humboldtallee 23, D-37073 Göttingen, Germany.
Sölter
Marion
M
Pieler
Tomas
T
D000595:Amino Acid Sequence; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D002453:Cell Cycle / Q000502:physiology*; D008565:Membrane Proteins / Q000378:metabolism; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009420:Nervous System / Q000196:embryology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D051880:Receptors, Notch; D015398:Signal Transduction / Q000502:physiology; D029867:Xenopus Proteins; D014982:Xenopus laevis / Q000196:embryology; D054462:p21-Activated Kinases
D051792:Basic Helix-Loop-Helix Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D017346:Protein Serine-Threonine Kinases; D051880:Receptors, Notch; D029867:Xenopus Proteins; D054462:p21-Activated Kinases; C101907:neurogenin, Xenopus