XB-ART-36654Dev Biol. December 1, 2007; 312 (1):
Identification of novel ciliogenesis factors using a new in vivo model for mucociliary epithelial development.
Mucociliary epithelia are essential for homeostasis of many organs and consist of mucus-secreting goblet cells and ciliated cells. Here, we present the ciliated epidermis of Xenopus embryos as a facile model system for in vivo molecular studies of mucociliary epithelial development. Using an in situ hybridization-based approach, we identified numerous genes expressed differentially in mucus-secreting cells or in ciliated cells. Focusing on genes expressed in ciliated cells, we have identified new candidate ciliogenesis factors, including several not present in the current ciliome. We find that TTC25-GFP is localized to the base of cilia and to ciliary axonemes, and disruption of TTC25 function disrupts ciliogenesis. Mig12-GFP localizes very strongly to the base of cilia and confocal imaging of this construct allows for simple visualization of the planar polarity of basal bodies that underlies polarized ciliary beating. Knockdown of Mig12 disrupts ciliogenesis. Finally, we show that ciliogenesis factors identified in the Xenopus epidermis are required in the midline to facilitate neural tube closure. These results provide further evidence of a requirement for cilia in neural tube morphogenesis and suggest that genes identified in the Xenopus epidermis play broad roles in ciliogenesis. The suites of genes identified here will provide a foundation for future studies, and may also contribute to our understanding of pathological changes in mucociliary epithelia that accompany diseases such as asthma.
Pubmed Id: 17961536
Article link: Dev Biol.
Grant support: R01 GM074104-03 NIGMS NIH HHS , R01 GM074104-04 NIGMS NIH HHS , R01 GM074104-04S1 NIGMS NIH HHS , R01 GM074104 NIGMS NIH HHS
Genes referenced: ap2a1 arcn1 c16orf80 capn2 cask cav1 cbfa2t2 ccdc11 ccdc19 ccdc78 ccna1 ccz1b cep57l1 cetn4 chfr chst9 crocc cyp27b1 dbp dcdc2b dhrs7 dlx3 dnaja1 e2f3 elovl7 flot2 foxa1 foxi1 fucolectin gata4 gdf11.2 glo1 hes4 il17ra itln1 laptm4a loc100490918 loc733461 lrmp lrrc1 mapk12 march5 med12 mid1ip1 noc4l nol8 notch1 nr2f2 odf2 odf3 otog paip2b pcdh8.2 ppargc1b prss27 ptrf rab11a rab18 rab28 rab6a rap1b rap2b rpe65 rsph1 runx1t1 sgce slc16a3 smtn sox11 stbd1 surf2 taf7 tead4 tekt3 tex15 trim29 ttc25 tuba4b tubb6 uap1 ubp1 usf1 vrk2 vti1a wsb2 xbp1 xpnpep3 zfand5 znf750
Antibodies referenced: Tuba4b Ab2 itln2 AB1
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