title: Bardet-Biedl syndrome genes are important in retrograde intracellular trafficking and Kupffer's vesicle cilia function.
abstract: Bardet-Biedl syndrome (BBS) is characterized by obesity, retinopathy, polydactyly, cognitive impairment, renal and cardiac anomalies as well as hypertension and diabetes. The nine known BBS genes do not appear to belong to the same functional category; yet mutation of these genes results in a nearly identical pleiotropic phenotype. Although the precise functions of the BBS proteins have yet to be determined, current data support a role in cilia function and intraflagellar transport. To gain insight into the biological processes controlled by BBS genes, we embarked on studies of six BBS orthologues from zebrafish. Knockdown of zebrafish bbs2, bbs4, bbs5, bbs6, bbs7 or bbs8 results in disruption of Kupffer's vesicle (KV), a ciliated organ thought to play a role in left-right patterning. KV defects are due to a progressive loss of cilia within the vesicle and result in subsequent alterations to organ laterality. We also note a specific defect altering retrograde melanosome transport. These studies are the first to comprehensively compare the diverse group of BBS genes in parallel and demonstrate a common role in intracellular trafficking, indicating that BBS proteins are involved in general organelle trafficking.
authors.affiliation: Howard Hughes Medical Institute, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Hsan-Jan
authors.initials: HJ
authors.lastname: Yen
authors.forename: Marwan K
authors.initials: MK
authors.lastname: Tayeh
authors.forename: Robert F
authors.initials: RF
authors.lastname: Mullins
authors.forename: Edwin M
authors.initials: EM
authors.lastname: Stone
authors.forename: Val C
authors.initials: VC
authors.lastname: Sheffield
authors.forename: Diane C
authors.initials: DC
authors.lastname: Slusarski
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D020788:Bardet-Biedl Syndrome / Q000235:genetics*; D019521:Body Patterning; D002110:Caffeine / Q000494:pharmacology; D002923:Cilia / Q000378:metabolism*; D003001:Cloning, Molecular; D004625:Embryo, Nonmammalian; D004837:Epinephrine / Q000494:pharmacology; D005123:Eye / Q000196:embryology / Q000648:ultrastructure; D005407:Flagella / Q000378:metabolism; D019084:Fluorescent Antibody Technique, Indirect; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D007150:Immunohistochemistry; D020460:Melanosomes / Q000187:drug effects / Q000378:metabolism; D018613:Microscopy, Confocal; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics / Q000378:metabolism; D029961:Zebrafish Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D016376:Oligonucleotides, Antisense; D029961:Zebrafish Proteins; D002110:Caffeine; D004837:Epinephrine