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Development 2016 Mar 01;1435:831-40. doi: 10.1242/dev.129551.
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The Lhx9-integrin pathway is essential for positioning of the proepicardial organ.

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

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: [+]

Species referenced: Xenopus laevis
Genes referenced: dag1 fn1 itga4 itgb1 lama1 lhx2 lhx9 psmd6 pxn tbx18 tcf21 tpm1 vcam1 wt1
GO keywords: 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, The bHLH transcription factor Tcf21 is required for lineage-specific EMT of cardiac fibroblast progenitors. 2012, Pubmed