| Literature DB >> 34903892 |
Emmanuelle Szenker-Ravi1, Tim Ott2, Muznah Khatoo3, Anne Moreau de Bellaing4, Wei Xuan Goh3, Yan Ling Chong5,6, Anja Beckers7,8, Darshini Kannesan3, Guillaume Louvel9,10, Priyanka Anujan5,11, Vydianathan Ravi5, Carine Bonnard12, Sébastien Moutton13, Patric Schoen14, Mélanie Fradin15, Estelle Colin16, André Megarbane17,18, Linda Daou19, Ghassan Chehab19,20, Sylvie Di Filippo21, Caroline Rooryck22, Jean-François Deleuze23, Anne Boland23, Nicolas Arribard24, Rukiye Eker25, Sumanty Tohari5, Alvin Yu-Jin Ng26, Marlène Rio27,28, Chun Teck Lim29,30, Birgit Eisenhaber29,31, Frank Eisenhaber29,31,32, Byrappa Venkatesh5,33, Jeanne Amiel27,34, Hugues Roest Crollius9, Christopher T Gordon34, Achim Gossler7,8, Sudipto Roy5,33,35, Tania Attie-Bitach27,36, Martin Blum37, Patrice Bouvagnet38, Bruno Reversade39,40,41,42.
Abstract
The vertebrate left-right axis is specified during embryogenesis by a transient organ: the left-right organizer (LRO). Species including fish, amphibians, rodents and humans deploy motile cilia in the LRO to break bilateral symmetry, while reptiles, birds, even-toed mammals and cetaceans are believed to have LROs without motile cilia. We searched for genes whose loss during vertebrate evolution follows this pattern and identified five genes encoding extracellular proteins, including a putative protease with hitherto unknown functions that we named ciliated left-right organizer metallopeptide (CIROP). Here, we show that CIROP is specifically expressed in ciliated LROs. In zebrafish and Xenopus, CIROP is required solely on the left side, downstream of the leftward flow, but upstream of DAND5, the first asymmetrically expressed gene. We further ascertained 21 human patients with loss-of-function CIROP mutations presenting with recessive situs anomalies. Our findings posit the existence of an ancestral genetic module that has twice disappeared during vertebrate evolution but remains essential for distinguishing left from right in humans.Entities:
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Year: 2021 PMID： 34903892 DOI： 10.1038/s41588-021-00970-4
Source DB: PubMed Journal: Nat Genet ISSN： 1061-4036 Impact factor: 41.307