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.
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http://dx.doi.org/10.1016/j.ydbio.2016.11.019 | DOI Listing |
Int J Biol Sci
January 2025
Department of Basic & Translational Sciences, School of Dental Medicine, University of Pennsylvania, USA.
Inositol polyphosphate-5-phosphatase E (INPP5E) is a 5-phosphatase critically involved in diverse physiological processes, including embryonic development, neurological function, immune regulation, hemopoietic cell dynamics, and macrophage proliferation, differentiation, and phagocytosis. Mutations in cause Joubert and Meckel-Gruber syndromes in humans; these are characterized by brain malformations, microphthalmia, situs inversus, skeletal abnormalities, and polydactyly. Recent studies have demonstrated the key role of INPP5E in governing intracellular processes like endocytosis, exocytosis, vesicular trafficking, and membrane dynamics.
View Article and Find Full Text PDFDev Biol
January 2025
Department of Molecular, Cellular and Development Biology, University of Colorado, Boulder, CO, 80309, USA. Electronic address:
Folic acid (FA) supplementation is a potent tool to reduce devastating birth defects known as neural tube defects (NTDs). Though effective, questions remain how FA achieves its protective effect and which gene mutations are sensitive to folic acid levels. We explore the relationship between FA dosage and NTD rates using NTD mouse models.
View Article and Find Full Text PDFHum Mol Genet
December 2024
Department of Human Genetics, McGill University, 3640 rue University, Montreal, QC, H3A 0C7, Canada.
Background: Primary ciliopathies are a heterogeneous group of rare disorders predominantly caused by autosomal-recessive genetic variants that disrupt non-motile ciliary function. They often manifest as a syndromic phenotype, frequently involving the kidney. Biallelic pathogenic variants in C2CD3 disrupt ciliogenesis and Sonic Hedgehog (SHH) signaling, resulting in a severe ciliopathy (Orofaciodigital syndrome XIV, OMIM 615948).
View Article and Find Full Text PDFPhysiol Res
November 2024
Department of Histology and Embryology, 2nd Faculty of Medicine, Charles University, Prague, Czech Republic.
Sci Rep
November 2024
Department of Chemistry and Molecular Biology, University of Gothenburg, Gothenburg, 41390, Sweden.
Male infertility presents a substantial challenge in reproductive medicine, often attributed to impaired sperm motility. The present study investigates the role of CCDC28A, a protein expressed specifically in male germ cells, whose paralog CCDC28B has been implicated in ciliogenesis. We identify unique expression patterns for CCDC28A and CCDC28B within the mouse testes, where CCDC28A is expressed in germ cells, whereas CCDC28B is expressed in supporting somatic cells.
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