The Role of Sp1 Family Genes in Wnt Mediated Neural Plate Patterning
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Wnt signaling has a conserved role in anterior-posterior (A-P) patterning of the remarkably complex vertebrate brain from a very basic primordium, the neural plate, by differentially regulating downstream target genes to induce distinct neural fates. Wnt proteins originate from the blastoderm margin and diffuse anteriorly to re-pattern the default state of the anterior neural tissue to more posterior fates. How this graded Wnt ligand in the neural plate is translated by responding cells to establish specific cell fate zones along the A-P axis is not well established. In order to understand neural patterning by Wnt better, we need to identify the downstream components of this pathway, for instance, the transcriptional targets of Wnt signaling and their subsequent roles. Two well known but less studied targets of Wnt/β-catenin signaling in Zebrafish, the sp5a and sp5-like (sp5l) genes, are good models to study induction of transcription factors and gene regulatory network that drives neural posteriorization downstream of Wnt signaling because these paralogous genes potentially play an important role in mediating Wnt-dependent posterior neural plate patterning. Results from our recent RNA sequencing analysis identifies another gene, sp8b, along with the sp5a and sp5l genes, that may also play a role in Wnt dependent patterning in the nervous system. These Wnt target genes encode zinc finger transcription factors (TFs) belonging to the Sp1 gene family and transcriptional regulation of sp5 orthologs by Wnt signaling is known to be conserved in vertebrates. In spite of the compelling evidence of a significant and evolutionarily conserved relation between the sp5 genes and Wnt signaling in vertebrates, the function of these genes and how they are regulated by the Wnt pathway to pattern the vertebrate brain is not understood properly. This thesis is aimed at understanding the in-vivo function of the sp5 an sp8b genes by generating zebrafish genetic mutants.
Mohanty, Saurav (2017). The Role of Sp1 Family Genes in Wnt Mediated Neural Plate Patterning. Master's thesis, Texas A & M University. Available electronically from