Identification of Pax2-regulated genes by expression profiling of the mid-hindbrain organizer region.
2005
The paired domain transcription factor Pax2 is required for the formation
of the isthmic organizer (IsO) at the midbrain-hindbrain boundary, where it
initiates expression of the IsO signal Fgf8. To gain further insight into the
role of Pax2 in mid-hindbrain patterning, we searched for novel Pax2-regulated
genes by cDNA microarray analysis of FACS-sorted GFP + mid-hindbrain
cells from wild-type and Pax2 –/– embryos
carrying a Pax2 GFP BAC transgene. Here, we report the
identification of five genes that depend on Pax2 function for their expression
in the mid-hindbrain boundary region. These genes code for the transcription
factors En2 and Brn1 (Pou3f3), the intracellular signaling modifiers Sef and
Tapp1, and the non-coding RNA Ncrms . The Brn1 gene was
further identified as a direct target of Pax2, as two functional Pax2-binding
sites in the promoter and in an upstream regulatory element of Brn1
were essential for lacZ transgene expression at the mid-hindbrain
boundary. Moreover, ectopic expression of a dominant-negative Brn1 protein in
chick embryos implicated Brn1 in Fgf8 gene regulation. Together,
these data defined novel functions of Pax2 in the establishment of distinct
transcriptional programs and in the control of intracellular signaling during
mid-hindbrain development.
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