PMID:21430154

Citation	Alvarado, DM, Hawkins, RD, Bashiardes, S, Veile, RA, Ku, YC, Powder, KE, Spriggs, MK, Speck, JD, Warchol, ME and Lovett, M (2011) An RNA interference-based screen of transcription factor genes identifies pathways necessary for sensory regeneration in the avian inner ear. J. Neurosci. 31:4535-43
Abstract	Sensory hair cells of the inner ear are the mechanoelectric transducers of sound and head motion. In mammals, damage to sensory hair cells leads to hearing or balance deficits. Nonmammalian vertebrates such as birds can regenerate hair cells after injury. In a previous study, we characterized transcription factor gene expression during chicken hair cell regeneration. In those studies, a laser microbeam or ototoxic antibiotics were used to damage the sensory epithelia (SE). The current study focused on 27 genes that were upregulated in regenerating SEs compared to untreated SEs in the previous study. Those genes were knocked down by siRNA to determine their requirement for supporting cell proliferation and to measure resulting changes in the larger network of gene expression. We identified 11 genes necessary for proliferation and also identified novel interactive relationships between many of them. Defined components of the WNT, PAX, and AP1 pathways were shown to be required for supporting cell proliferation. These pathways intersect on WNT4, which is also necessary for proliferation. Among the required genes, the CCAAT enhancer binding protein, CEBPG, acts downstream of Jun Kinase and JUND in the AP1 pathway. The WNT coreceptor LRP5 acts downstream of CEBPG, as does the transcription factor BTAF1. Both of these genes are also necessary for supporting cell proliferation. This is the first large-scale screen of its type and suggests an important intersection between the AP1 pathway, the PAX pathway, and WNT signaling in the regulation of supporting cell proliferation during inner ear hair cell regeneration.
Links	PubMed PMC3086586 Online version:10.1523/JNEUROSCI.5456-10.2011
Keywords	Animals; CCAAT-Binding Factor/genetics; CCAAT-Binding Factor/physiology; Cell Proliferation; Chickens; Ear, Inner/physiology; Epithelium/physiology; Gene Knockdown Techniques; Hair Cells, Auditory, Inner/physiology; JNK Mitogen-Activated Protein Kinases/antagonists & inhibitors; JNK Mitogen-Activated Protein Kinases/physiology; Lasers; Microarray Analysis; Nerve Regeneration/physiology; Paxillin/genetics; Paxillin/physiology; RNA Interference/physiology; Saccule and Utricle/physiology; Signal Transduction/genetics; Signal Transduction/physiology; Transcription Factor AP-1/genetics; Transcription Factor AP-1/physiology; Transcription Factor TFIID/genetics; Transcription Factor TFIID/physiology; Transcription Factors/genetics; Wnt Proteins/genetics; Wnt Proteins/pharmacology; Wnt Proteins/physiology; Wnt4 Protein
edit table

Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
CHICK:Q9PTX1		GO:0008283: cell proliferation	ECO:0000315:		P		Figure 3b is showing that the pax2 and pax5 are inhibiting supporting cell proliferation while pax3 and pax7 have no significant effect on proliferation.	complete CACAO 12480
CHICK:Q9W601		GO:0008283: cell proliferation	ECO:0000315:		P		Figure 3b is showing that the pax2 and pax5 are inhibiting supporting cell proliferation while pax3 and pax7 have no significant effect on proliferation.	complete CACAO 12747

References

See Help:References for how to manage references in GONUTS.