Spalt-like 4 promotes posterior neural fates via repression of pou5f3 family members in Xenopus.
Amphibian neural development occurs as a two-step process: (1) induction specifies a neural fate in undifferentiated ectoderm; and (2) transformation induces posterior spinal cord and hindbrain. Signaling through the Fgf, retinoic acid (RA) and Wnt/β-catenin pathways is necessary and sufficient to induce posterior fates in the neural plate, yet a mechanistic understanding of the process is lacking. Here, we screened for factors enriched in posterior neural tissue and identify spalt-like 4 (sall4), which is induced by Fgf. Knockdown of Sall4 results in loss of spinal cord marker expression and increased expression of pou5f3.2 (oct25), pou5f3.3 (oct60) and pou5f3.1 (oct91) (collectively, pou5f3 genes), the closest Xenopus homologs of mammalian stem cell factor Pou5f1 (Oct4). Overexpression of the pou5f3 genes results in the loss of spinal cord identity and knockdown of pou5f3 function restores spinal cord marker expression in Sall4 morphants. Finally, knockdown of Sall4 blocks the posteriorizing effects of Fgf and RA signaling in the neurectoderm. These results suggest that Sall4, activated by posteriorizing signals, represses the pou5f3 genes to provide a permissive environment allowing for additional Wnt/Fgf/RA signals to posteriorize the neural plate.
Department of Molecular & Cell Biology, University of California, Berkeley, CA 94720, USA.
John J
JJ
Young
Rachel A S
RA
Kjolby
Nikki R
NR
Kong
Stefanie D
SD
Monica
Richard M
RM
Harland
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D019521:Body Patterning / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D019070:Cell Lineage / Q000187:drug effects / Q000235:genetics; D004625:Embryo, Nonmammalian / Q000187:drug effects / Q000378:metabolism; D005346:Fibroblast Growth Factors / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D005820:Genetic Testing; D060172:Morpholinos / Q000494:pharmacology; D054258:Neural Plate / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D012249:Rhombencephalon / Q000378:metabolism; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects / Q000196:embryology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D014212:Tretinoin / Q000494:pharmacology; D060449:Wnt Signaling Pathway / Q000187:drug effects / Q000235:genetics; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis / Q000196:embryology / Q000235:genetics / Q000378:metabolism*
D015415:Biomarkers; D060172:Morpholinos; D012097:Repressor Proteins; C503712:SALL4 protein, Xenopus; D014157:Transcription Factors; D029867:Xenopus Proteins; D014212:Tretinoin; D005346:Fibroblast Growth Factors
Gene regulation; Neural patterning; Oct4; Sall4; Xenopus