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Elife 2016 Aug 31;5. doi: 10.7554/eLife.17666.
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Dissecting the pre-placodal transcriptome to reveal presumptive direct targets of Six1 and Eya1 in cranial placodes.

Riddiford N , Schlosser G .

The pre-placodal ectoderm, marked by the expression of the transcription factor Six1 and its co-activator Eya1, develops into placodes and ultimately into many cranial sensory organs and ganglia. Using RNA-Seq in Xenopus laevis we screened for presumptive direct placodal target genes of Six1 and Eya1 by overexpressing hormone-inducible constructs of Six1 and Eya1 in pre-placodal explants, and blocking protein synthesis before hormone-inducing nuclear translocation of Six1 or Eya1. Comparing the transcriptome of explants with non-induced controls, we identified hundreds of novel Six1/Eya1 target genes with potentially important roles for placode development. Loss-of-function studies confirmed that target genes encoding known transcriptional regulators of progenitor fates (e.g. Sox2, Hes8) and neuronal/sensory differentiation (e.g. Ngn1, Atoh1, Pou4f1, Gfi1) require Six1 and Eya1 for their placodal expression. Our findings provide insights into the gene regulatory network regulating placodal neurogenesis downstream of Six1 and Eya1 suggesting new avenues of research into placode development and disease.

PubMed ID: 27576864
PMC ID: PMC5035141
Article link: Elife

Species referenced: Xenopus laevis
Genes referenced: atoh1 crem emx1 eya1 fosb foxd3 gad1.2 gfi1 hes2 hes5.2 hes5.4 hes5.6 hes5.7 isl1 isl2 lhx5 mab21l2 neurog1 pou3f2 pou4f1 pou4f4 ripply3 sim1 six1 sox2 sox21 sox3 tbx15 tbx6 tlx1
Morpholinos: eya1 MO1 eya1 MO2 six1 MO1 six1 MO2

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References [+] :
Abdolazimi, Selection of cell fate in the organ of Corti involves the integration of Hes/Hey signaling at the Atoh1 promoter. 2016, Pubmed