title: Identification of FOXJ1 effectors during ciliogenesis in the foetal respiratory epithelium and embryonic left-right organiser of the mouse.
abstract: Formation of motile cilia in vertebrate embryos is essential for proper development and tissue function. Key regulators of motile ciliogenesis are the transcription factors FOXJ1 and NOTO, which are conserved throughout vertebrates. Downstream target genes of FOXJ1 have been identified in a variety of species, organs and cultured cell lines; in murine embryonic and foetal tissues, however, FOXJ1 and NOTO effectors have not been comprehensively analysed and our knowledge of the downstream genetic programme driving motile ciliogenesis in the mammalian lung and ventral node is fragmentary. We compared genome-wide expression profiles of undifferentiated E14.5 vs. abundantly ciliated E18.5 micro-dissected airway epithelia as well as Foxj1+vs. Foxj1-deficient foetal (E16.5) lungs of the mouse using microarray hybridisation. 326 genes deregulated in both screens are candidates for FOXJ1-dependent, ciliogenesis-associated factors at the endogenous onset of motile ciliogenesis in the lung, including 123 genes that have not been linked to ciliogenesis before; 46% of these novel factors lack known homologues outside mammals. Microarray screening of Noto+vs. Noto null early headfold embryos (E7.75) identified 59 of the lung candidates as NOTO/FOXJ1-dependent factors in the embryonic left-right organiser that carries a different subtype of motile cilia. For several uncharacterised factors from this small overlap - including 1700012B09Rik, 1700026L06Rik and Fam183b - we provide extended experimental evidence for a ciliary function.
authors.affiliation: Institut für Molekularbiologie, OE 5250, Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, 30625 Hannover, Germany. Electronic address: Stauber.Michael@mh-hannover.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Stauber
authors.affiliation: Institut für Molekularbiologie, OE 5250, Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
authors.forename: Marina
authors.initials: M
authors.lastname: Weidemann
authors.affiliation: Institut für Physiologische Chemie, OE 4310, Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Dittrich-Breiholz
authors.affiliation: Institut für Molekularbiologie, OE 5250, Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Lobschat
authors.affiliation: Institut für Molekularbiologie, OE 5250, Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
authors.forename: Leonie
authors.initials: L
authors.lastname: Alten
authors.affiliation: Institut für Molekularbiologie, OE 5250, Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
authors.forename: Michaela
authors.initials: M
authors.lastname: Mai
authors.affiliation: Institut für Molekularbiologie, OE 5250, Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Beckers
authors.affiliation: Rudolf-Buchheim-Institut für Pharmakologie, Justus-Liebig-Universität Gießen, Schubertstr. 81, 35392 Gießen, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Kracht
authors.affiliation: Institut für Molekularbiologie, OE 5250, Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
authors.forename: Achim
authors.initials: A
authors.lastname: Gossler
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D002923:Cilia / Q000378:metabolism*; D015536:Down-Regulation / Q000235:genetics; D005333:Fetus / Q000378:metabolism*; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D063990:Gene Ontology; D056726:Genetic Association Studies; D016678:Genome; D049452:Green Fluorescent Proteins / Q000378:metabolism; D008168:Lung / Q000196:embryology / Q000378:metabolism; D051379:Mice; D009928:Organ Specificity / Q000235:genetics; D020897:Organizers, Embryonic / Q000378:metabolism*; D038081:Organogenesis / Q000235:genetics; D015203:Reproducibility of Results; D020545:Respiratory Mucosa / Q000166:cytology / Q000196:embryology*; D013347:Subcellular Fractions / Q000378:metabolism; D059467:Transcriptome / Q000235:genetics
chemical_list: C481963:FOXJ1 protein, mouse; D051858:Forkhead Transcription Factors; D049452:Green Fluorescent Proteins
keywords: Foxj1; IMCD3 cell line; Motile cilium; Noto; Respiratory epithelium; Ventral node