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.
Hayes
Julie M
JM
Department of Molecular Cell and Developmental Biology, and Institute for Cellular and Molecular Biology, University Station C1000, University of Texas, Austin, TX 78712, USA.
Kim
Su Kyoung
SK
Abitua
Philip B
PB
Park
Tae Joo
TJ
Herrington
Emily R
ER
Kitayama
Atsushi
A
Grow
Matthew W
MW
Ueno
Naoto
N
Wallingford
John B
JB
D000818:Animals; D054468:Axoneme; D015415:Biomarkers; D002923:Cilia / Q000378:metabolism* / Q000648:ultrastructure; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000378:metabolism; D000078404:Epidermal Cells; D004817:Epidermis / Q000648:ultrastructure; D004848:Epithelium / Q000196:embryology* / Q000648:ultrastructure; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D020397:Goblet Cells; D006801:Humans; D008954:Models, Biological; D009092:Mucous Membrane / Q000196:embryology* / Q000378:metabolism*; D054259:Neural Tube; D021381:Protein Transport; D051880:Receptors, Notch; D015203:Reproducibility of Results; D014981:Xenopus / Q000196:embryology* / Q000235:genetics; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism*
D015415:Biomarkers; D051880:Receptors, Notch; D029867:Xenopus Proteins