title: Fibronectin mediates mesendodermal cell fate decisions.
abstract: Non-cell-autonomous signals often play crucial roles in cell fate decisions during animal development. Reciprocal signaling between endoderm and mesoderm is vital for embryonic development, yet the key signals and mechanisms remain unclear. Here, we show that endodermal cells efficiently promote the emergence of mesodermal cells in the neighboring population through signals containing an essential short-range component. The endoderm-mesoderm interaction promoted precardiac mesoderm formation in mouse embryonic stem cells and involved endodermal production of fibronectin. In vivo, fibronectin deficiency resulted in a dramatic reduction of mesoderm accompanied by endodermal expansion in zebrafish embryos. This event was mediated by regulation of Wnt signaling in mesodermal cells through activation of integrin-β1. Our findings highlight the importance of the extracellular matrix in mediating short-range signals and reveal a novel function of endoderm, involving fibronectin and its downstream signaling cascades, in promoting the emergence of mesoderm.
authors.affiliation: Gladstone Institute of Cardiovascular Disease, San Francisco, CA 94158, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Cheng
authors.forename: Peter
authors.initials: P
authors.lastname: Andersen
authors.forename: David
authors.initials: D
authors.lastname: Hassel
authors.forename: Bogac L
authors.initials: BL
authors.lastname: Kaynak
authors.forename: Pattraranee
authors.initials: P
authors.lastname: Limphong
authors.forename: Lonny
authors.initials: L
authors.lastname: Juergensen
authors.forename: Chulan
authors.initials: C
authors.lastname: Kwon
authors.forename: Deepak
authors.initials: D
authors.lastname: Srivastava
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D018920:Coculture Techniques; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D004627:Embryonic Induction; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D004707:Endoderm / Q000166:cytology / Q000378:metabolism*; D005109:Extracellular Matrix / Q000235:genetics / Q000378:metabolism; D005326:Fetal Proteins / Q000235:genetics / Q000378:metabolism; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D019012:Integrin beta1 / Q000235:genetics / Q000378:metabolism; D008648:Mesoderm / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D020825:T-Box Domain Proteins / Q000235:genetics / Q000378:metabolism; D060449:Wnt Signaling Pathway; D015027:Zebrafish / Q000196:embryology / Q000378:metabolism; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism; D000098908:Brachyury Protein
chemical_list: D005326:Fetal Proteins; D005353:Fibronectins; D019012:Integrin beta1; D034741:RNA, Small Interfering; D020825:T-Box Domain Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin; D000098908:Brachyury Protein; C495267:CTNNB1 protein, mouse
keywords: Endoderm; Fibronectin; Integrin-β1; Mesoderm; Wnt