nlz1 is required for cilia formation in zebrafish embryogenesis.
The formation of cilia is a fundamental developmental process affecting diverse functions such as cellular signaling, tissue morphogenesis and body patterning. However, the mechanisms of ciliogenesis during vertebrate development are not fully understood. In this report we describe a novel role of the Nlz1 protein in ciliogenesis. We demonstrate morpholino-mediated knockdown of nlz1 in zebrafish causes abnormal specification of the cells of Kupffer's vesicle (KV); a severe reduction of the number of cilia in KV, the pronephros, and the neural floorplate; and a spectrum of later phenotypes reminiscent of human ciliopathies. In vitro and in vivo data indicate that Nlz1 acts downstream of Foxj1a and Wnt8a/presumed canonical Wnt signaling. Furthermore, Nlz1 contributes to motile cilia formation by positively regulating Wnt11/presumed non-canonical Wnt signaling. Together, our data suggest a novel role of nlz1 in ciliogenesis and the morphogenesis of multiple tissues.
Unit on Pediatric, Developmental & Genetic Ophthalmology, Ophthalmic Genetics and Visual Function Branch, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Sunit
S
Dutta
Unit on Pediatric, Developmental & Genetic Ophthalmology, Ophthalmic Genetics and Visual Function Branch, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Shahila
S
Sriskanda
Unit on Pediatric, Developmental & Genetic Ophthalmology, Ophthalmic Genetics and Visual Function Branch, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Elangovan
E
Boobalan
Unit on Pediatric, Developmental & Genetic Ophthalmology, Ophthalmic Genetics and Visual Function Branch, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Ramakrishna P
RP
Alur
Microarray Core, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Abdel
A
Elkahloun
Unit on Pediatric, Developmental & Genetic Ophthalmology, Ophthalmic Genetics and Visual Function Branch, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Brian P
BP
Brooks
D000423:Alcian Blue; D000818:Animals; D015153:Blotting, Western; D002923:Cilia / Q000502:physiology*; D017931:DNA Primers / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D051858:Forkhead Transcription Factors / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D017403:In Situ Hybridization; D008156:Luciferases; D018613:Microscopy, Confocal; D009024:Morphogenesis / Q000502:physiology*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051153:Wnt Proteins / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000502:physiology*; D015027:Zebrafish / Q000196:embryology*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
D017931:DNA Primers; D004268:DNA-Binding Proteins; D051858:Forkhead Transcription Factors; C533681:Foxj1a protein, zebrafish; D051153:Wnt Proteins; C092568:Wnt11 protein, zebrafish; D029961:Zebrafish Proteins; C435747:znf703 protein, zebrafish; D008156:Luciferases; D000423:Alcian Blue
Coloboma; Foxj1; Kupffer's vesicle; Left–right asymmetry; Motile cilia; Nlz1; Wnt