Xiro homeoproteins coordinate cell cycle exit and primary neuron formation by upregulating neuronal-fate repressors and downregulating the cell-cycle inhibitor XGadd45-gamma.
The iroquois (iro) homeobox genes participate in many developmental processes both in vertebrates and invertebrates, among them are neural plate formation and neural patterning. In this work, we study in detail Xenopus Iro (Xiro) function in primary neurogenesis. We show that misexpression of Xiro genes promotes the activation of the proneural gene Xngnr1 but suppresses neuronal differentiation. This is probably due to upregulation of at least two neuronal-fate repressors: XHairy2A and XZic2. Accordingly, primary neurons arise at the border of the Xiro expression domains. In addition, we identify XGadd45-gamma as a new gene repressed by Xiro. XGadd45-gamma encodes a cell-cycle inhibitor and is expressed in territories where cells will exit mitosis, such as those where primary neurons arise. Indeed, XGadd45-gamma misexpression causes cell cycle arrest. We conclude that, during Xenopus primary neuron formation, in Xiro expressing territories neuronal differentiation is impaired, while in adjacent cells, XGadd45-gamma may help cells stop dividing and differentiate as neurons.
de la Calle-Mustienes
Elisa
E
Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas and Universidad Autónoma de Madrid, Cantoblanco, 28049 Madrid, Spain.
Glavic
Alvaro
A
Modolell
Juan
J
Gómez-Skarmeta
José Luis
JL
D000595:Amino Acid Sequence; D000818:Animals; D002453:Cell Cycle; D002454:Cell Differentiation; D002455:Cell Division; D003513:Cycloheximide / Q000494:pharmacology; D018076:DNA, Complementary / Q000378:metabolism; D015536:Down-Regulation; D018507:Gene Expression Regulation, Developmental; D017403:In Situ Hybridization; D020287:In Situ Nick-End Labeling; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000378:metabolism; D008954:Models, Biological; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins; D009474:Neurons / Q000378:metabolism*; D010957:Plasmids / Q000378:metabolism; D014176:Protein Biosynthesis; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011506:Proteins; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051880:Receptors, Notch; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism* / Q000502:physiology*; D015854:Up-Regulation; D014981:Xenopus; D029867:Xenopus Proteins; D000097642:GADD45 Proteins
D003513:Cycloheximide; D018076:DNA, Complementary; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D011500:Protein Synthesis Inhibitors; D011506:Proteins; D012313:RNA; D012333:RNA, Messenger; D051880:Receptors, Notch; D014157:Transcription Factors; D029867:Xenopus Proteins; D000097642:GADD45 Proteins; C110460:IRX2 protein, Xenopus; C484675:Xiro1 protein, Xenopus