title: Notch signaling can inhibit Xath5 function in the neural plate and developing retina.
abstract: Neuronal differentiation is regulated by both positive and negative regulatory factors; however, precisely how these factors interact to regulate retinogenesis is still unclear. We have examined the ability of the Notch pathway to modulate the function of the basic helix-loop-helix factor Xath5. Overexpression of Xath5 by RNA injection into cleavage-stage blastomeres promotes ectopic neurogenesis at neural plate stages and ganglion cell differentiation in the developing retina. We found that these activities of Xath5 could be inhibited by coexpression of activated Notch. Notch inhibition of Xath5 function was reversed by coexpression with the zinc finger protein X-MyT1. The Notch effector enhancer-of-split related 1 (ESR1) also blocked Xath5 activity but efficient inhibition by ESR1 required the DNA binding basic domain and the conserved WRPW motif. In addition, ESR1 inhibited the ability of Xath5 to directly activate the expression of XBrn3d, a transcription factor involved in retinal ganglion cell development. Xath5 could upregulate expression of X-Delta-1, ESR1, and ESR3, suggesting that Xath5 participates in a regulatory loop with the Notch pathway.
authors.affiliation: Department of Neurobiology and Anatomy, University of Utah, Salt Lake City 84132, USA.
authors.forename: M L
authors.initials: ML
authors.lastname: Schneider
authors.forename: D L
authors.initials: DL
authors.lastname: Turner
authors.forename: M L
authors.initials: ML
authors.lastname: Vetter
mesh_terms: D020816:Amino Acid Motifs / Q000235:genetics; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D001665:Binding Sites / Q000235:genetics; D001757:Blastomeres / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002490:Central Nervous System / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D049452:Green Fluorescent Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008164:Luminescent Proteins / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000494:pharmacology; D051880:Receptors, Notch; D012160:Retina / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014404:Tubulin / Q000378:metabolism; D029867:Xenopus Proteins; D014982:Xenopus laevis / Q000196:embryology* / Q000378:metabolism
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D005136:Eye Proteins; D005656:Fungal Proteins; D049452:Green Fluorescent Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008164:Luminescent Proteins; D008565:Membrane Proteins; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases; D012333:RNA, Messenger; D051880:Receptors, Notch; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D014404:Tubulin; D029867:Xenopus Proteins; C109416:ATOH7 protein, Xenopus; C095970:MYT1 kinase, Xenopus; C088937:MEC1 protein, S cerevisiae