Journal article
Integration of Nodal and BMP Signals in the Heart Requires FoxH1 to Create Left-Right Differences in Cell Migration Rates That Direct Cardiac Asymmetry
PLoS genetics, v 9(1), pp e1003109-e1003109
01 Jan 2013
PMID: 23358434
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Failure to properly establish the left-right (L/R) axis is a major cause of congenital heart defects in humans, but how L/R patterning of the embryo leads to asymmetric cardiac morphogenesis is still unclear. We find that asymmetric Nodal signaling on the left and Bmp signaling act in parallel to establish zebrafish cardiac laterality by modulating cell migration velocities across the L/R axis. Moreover, we demonstrate that Nodal plays the crucial role in generating asymmetry in the heart and that Bmp signaling via Bmp4 is dispensable in the presence of asymmetric Nodal signaling. In addition, we identify a previously unappreciated role for the Nodal-transcription factor FoxH1 in mediating cell responsiveness to Bmp, further linking the control of these two pathways in the heart. The interplay between these TGF beta pathways is complex, with Nodal signaling potentially acting to limit the response to Bmp pathway activation and the dosage of Bmp signals being critical to limit migration rates. These findings have implications for understanding the complex genetic interactions that lead to congenital heart disease in humans.
Metrics
Details
- Title
- Integration of Nodal and BMP Signals in the Heart Requires FoxH1 to Create Left-Right Differences in Cell Migration Rates That Direct Cardiac Asymmetry
- Creators
- Kari F. Lenhart - Princeton UniversityNathalia G. Holtzman - Queens College, CUNYJessica R. Williams - Princeton UniversityRebecca D. Burdine - Princeton University
- Publication Details
- PLoS genetics, v 9(1), pp e1003109-e1003109
- Publisher
- Public Library Science
- Number of pages
- 11
- Grant note
- 10-2409-CCR-EO / New Jersey Commission on Cancer Research IOS-1147123 / National Science Foundation; National Science Foundation (NSF) National Heart, Lung, and Blood Institute; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) R01HD048584 / EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD) 1147123 / Direct For Biological Sciences; National Science Foundation (NSF); NSF - Directorate for Biological Sciences (BIO) R15HL096067 / NATIONAL HEART, LUNG, AND BLOOD INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) 10PRE4180027 / American Heart Association R15HL096067 / Queens College Research Enhancement Funds 1R01HD048584 / National Institutes of Child Health and Human Development; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD) National Science Foundation Graduate Research Fellowship; National Science Foundation (NSF)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biology
- Web of Science ID
- WOS:000314651500003
- Scopus ID
- 2-s2.0-84873495850
- Other Identifier
- 991020099918104721
UN Sustainable Development Goals (SDGs)
This publication has contributed to the advancement of the following goals:
InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Genetics & Heredity