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XB-ART-51778
Development March 1, 2016; 143 (5): 831-40.

The Lhx9-integrin pathway is essential for positioning of the proepicardial organ.

Tandon P , Wilczewski CM , Williams CE , Conlon FL .


Abstract
The development of the vertebrate embryonic heart occurs by hyperplastic growth as well as the incorporation of cells from tissues outside of the initial heart field. Amongst these tissues is the epicardium, a cell structure that develops from the precursor proepicardial organ on the right side of the septum transversum caudal to the developing heart. During embryogenesis, cells of the proepicardial organ migrate, adhere and envelop the maturing heart, forming the epicardium. The cells of the epicardium then delaminate and incorporate into the heart giving rise to cardiac derivatives, including smooth muscle cells and cardiac fibroblasts. Here, we demonstrate that the LIM homeodomain protein Lhx9 is transiently expressed in Xenopus proepicardial cells and is essential for the position of the proepicardial organ on the septum transversum. Utilizing a small-molecule screen, we found that Lhx9 acts upstream of integrin-paxillin signaling and consistently demonstrate that either loss of Lhx9 or disruption of the integrin-paxillin pathway results in mis-positioning of the proepicardial organ and aberrant deposition of extracellular matrix proteins. This leads to a failure of proepicardial cell migration and adhesion to the heart, and eventual death of the embryo. Collectively, these studies establish a requirement for the Lhx9-integrin-paxillin pathway in proepicardial organ positioning and epicardial formation.

PubMed ID: 26811386
PMC ID: PMC4813339
Article link: Development
Grant support: P40 OD010997 NIH HHS , R21 HD073044 NICHD NIH HHS , R21HD073044 NICHD NIH HHS , R01 HL127640 NHLBI NIH HHS , T32 HL069768 NHLBI NIH HHS

Genes referenced: tbx18 lhx9 tcf21 wt1 pxn itgb1 itga4 fn1 tpm1 lama1 dag1 lhx2 vcam1
GO Terms: integrin-mediated signaling pathway [+]
Antibodies: Dag1 Ab3 Fn1 Ab6 Itgb1 Ab1 Lama1 Ab1 Pxn Ab2 Tpm1 Ab1
Morpholinos: lhx9 MO2 lhx9 MO3 lhx9 MO4


Article Images: [+] show captions
References:
Acharya, 2012, Pubmed [+]


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