sall1 and sall4 repress pou5f3 family expression to allow neural patterning, differentiation, and morphogenesis in Xenopus laevis.
The embryonic precursor of the vertebrate central nervous system, the neural plate, is patterned along the anterior-posterior axis and shaped by morphogenetic movements early in development. We previously identified the genes sall1 and sall4, known regulators of pluripotency in other contexts, as transcriptional targets of developmental signaling pathways that regulate neural development. Here, we demonstrate that these two genes are required for induction of posterior neural fates, the cell shape changes that contribute to neural tube closure, and later neurogenesis. Upon sall1 or sall4 knockdown, defects are associated with the failure of the neural plate to differentiate. Consistent with this, sall-deficient neural tissue exhibits an aberrant upregulation of pou5f3 family genes, the Xenopus homologs of the mammalian stem cell maintenance factor Pou5f1 (Oct4). Furthermore, overexpression of pou5f3 genes in Xenopus causes defects in neural patterning, morphogenesis, and differentiation that phenocopy those observed in sall1 and sall4 morphants. In all, this work shows that both sall1 and sall4 act to repress pou5f3 family gene expression in the neural plate, thereby allowing vertebrate neural development to proceed.
Department of Molecular & Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
Cameron R T
CRT
Exner
Department of Molecular & Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
Albert Y
AY
Kim
Department of Molecular & Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
Sarah M
SM
Mardjuki
Department of Molecular & Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA. Electronic address: harland@berkeley.edu.
Richard M
RM
Harland
D000818:Animals; D019521:Body Patterning / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D004625:Embryo, Nonmammalian / Q000196:embryology / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D017403:In Situ Hybridization; D018613:Microscopy, Confocal; D009024:Morphogenesis / Q000235:genetics; D054258:Neural Plate / Q000196:embryology / Q000378:metabolism*; D054261:Neurulation / Q000235:genetics; D050814:Octamer Transcription Factor-3 / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics*; D029867:Xenopus Proteins / Q000235:genetics*; D014982:Xenopus laevis / Q000196:embryology / Q000235:genetics*
D050814:Octamer Transcription Factor-3; C503712:SALL4 protein, Xenopus; C526197:Sall1 protein, Xenopus; D014157:Transcription Factors; D029867:Xenopus Proteins
Hingepoint cells; Neural patterning; Neural tube morphogenesis; Oct4; pou5f1