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Published July 1, 2013 | Published
Journal Article Open

Laminin β1a controls distinct steps during the establishment of digestive organ laterality

Abstract

Visceral organs, including the liver and pancreas, adopt asymmetric positions to ensure proper function. Yet the molecular and cellular mechanisms controlling organ laterality are not well understood. We identified a mutation affecting zebrafish laminin β1a (lamb1a) that disrupts left-right asymmetry of the liver and pancreas. In these mutants, the liver spans the midline and the ventral pancreatic bud remains split into bilateral structures. We show that lamb1a regulates asymmetric left-right gene expression in the lateral plate mesoderm (LPM). In particular, lamb1a functions in Kupffer's vesicle (KV), a ciliated organ analogous to the mouse node, to control the length and function of the KV cilia. Later during gut-looping stages, dynamic expression of Lamb1a is required for the bilayered organization and asymmetric migration of the LPM. Loss of Lamb1a function also results in aberrant protrusion of LPM cells into the gut. Collectively, our results provide cellular and molecular mechanisms by which extracellular matrix proteins regulate left-right organ morphogenesis.

Additional Information

© 2013 The Company of Biologists Ltd. Accepted April 22, 2013. We thank Elke Ober, Holly Field, Heather Verkade and other members of the ENU screen team, as well as Chantilly (Munson) Apollon for sharing reagents and expertise in LR organ asymmetry. We thank Mike Parsons for the grumpy allele and Thai Truong for assistance with settings for live imaging of the KV flow. Thanks to Zhaoxia Sun for sharing before publication her protocol for the analysis of KV flow, and to Pablo Oteíza and Hiroaki Ishikawa for advice. Funding: T.H.-H. was supported by a Pew Latin American Fellowship in the Biomedical Sciences and by a California Institute for Regenerative Medicine Training Grant [T2-00006]. C.Y. is supported by an National Institutes of Health (NIH) K99 Award [AA020514], a University of California at San Francisco Liver Center Pilot/Feasibility Award [NIH P30DK026743] and the Cincinnati Children's Hospital Research Foundation. This work was supported in part by grants from the NIH [P50 HG004071 to M.E.B., R01DK060322 to D.Y.R.S.] and from the Packard Foundation (to D.Y.R.S.). Deposited in PMC for release after 12 months. Author contributions: T.H.-H. and C.Y. designed and performed experiments, analyzed data and wrote the manuscript. D.E.S.K. performed experiments, analyzed data and edited the manuscript. M.E.B. and D.Y.R.S. supervised the work, including helping with experimental design, data, analysis and manuscript preparation.

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Created:
August 22, 2023
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October 24, 2023