Does IRF6 Work Alone?
Take the reading one piece at a time. For each piece: read it once, underline the sentence that says what happens, then look up any word in the list. Tap a word to see its definition.
Piece 1 of 2
Read five real findings before looking at the diagram. Clue A: most Van der Woude syndrome (cleft plus lip pits) is caused by loss-of-function variants in IRF6. Clue B: a smaller set of Van der Woude families have no IRF6 mutation but instead carry mutations in GRHL3, which causes the same periderm and cleft problem. Clue C: in zebrafish and mouse, turning IRF6 off lowers the expression of GRHL3 and of KLF17 (fish) or KLF4 (mouse), and forcing IRF6 back on brings those genes back up. Clue D: the transcription factor p63 (TP63) sits above IRF6 and is needed to keep IRF6 switched on in the epithelium. Clue E: a newly reported cause of Van der Woude is loss of PRKCI, which acts upstream of IRF6.
Piece 2 of 2
The circuit to reconstruct is: upstream signals (including PRKCI) feed a hidden node that keeps IRF6 on; IRF6 partners with GRHL3, and either one failing causes the disease; IRF6 then drives KLF4 and KLF17 downstream. The hidden node is the gene in Clue D.
Reading the Research
- Skim the title and abstract first to get the gist.
- Circle the one sentence that states the main claim.
- Box the evidence the authors give for that claim.
- Mark one sentence that confuses you, and move on.
Now put it together: In one or two sentences, say what this whole reading is telling you about Mateo. Then go back to the lesson and fill in the guided notes.