title: Prokineticin-1 modulates proliferation and differentiation of enteric neural crest cells.
abstract: Prokineticins (Prok-1 and Prok-2) belong to a newly identified AVIT protein family. They are involved in variety of activities in various tissues, including smooth muscle contraction of the gastrointestinal tract and promoting proliferation of endothelial cells derived from adrenal gland. Importantly, they also act as the survival factors to modulate growth and survival of neurons and hematopoietic stem cells. In this study we demonstrated that Prok-1 (but not Prok-2) protein is expressed in the mucosa and mesenchyme of the mouse embryonic gut during enteric nervous system development. Its receptor, PK-R1 is expressed in the enteric neural crest cells (NCCs). To elucidate the physiological role(s) of Prok-1 in NCCs, we isolated the NCCs from the mouse embryonic gut (E11.5) and cultured them in the form of neurospheres. In an in vitro NCC culture, Prok-1 was able to activate both Akt and MAPK pathways and induce the proliferation and differentiation (but not migration) of NCCs via PK-R1. Knock-down of PK-R1 using siRNA resulted in a complete abolishment of Prok-1 induced proliferation. Taken together, it is the first report demonstrating that Prok-1 acts as a gut mucosa/mesenchyme-derived factor and maintains proliferation and differentiation of enteric NCCs.
authors.affiliation: Department of Surgery, University of Hong Kong, Pokfulam, Faculty of Medicine Building, 21 Sassoon Road, Hong Kong, SAR, China. engan@hkucc.hku.hk
authors.forename: Elly S W
authors.initials: ES
authors.lastname: Ngan
authors.forename: K Y
authors.initials: KY
authors.lastname: Lee
authors.forename: Francesco Y L
authors.initials: FY
authors.lastname: Sit
authors.forename: H C
authors.initials: HC
authors.lastname: Poon
authors.forename: Jacqueline K Y
authors.initials: JK
authors.lastname: Chan
authors.forename: M H
authors.initials: MH
authors.lastname: Sham
authors.forename: Vincent C H
authors.initials: VC
authors.lastname: Lui
authors.forename: Paul K H
authors.initials: PK
authors.lastname: Tam
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D005753:Gastric Mucosa / Q000166:cytology / Q000378:metabolism; D041981:Gastrointestinal Tract / Q000166:cytology* / Q000196:embryology / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D008648:Mesoderm / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009432:Neural Crest / Q000166:cytology* / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D021381:Protein Transport; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism; D042662:Vascular Endothelial Growth Factor, Endocrine-Gland-Derived / Q000235:genetics / Q000378:metabolism*
chemical_list: D043562:Receptors, G-Protein-Coupled; D042662:Vascular Endothelial Growth Factor, Endocrine-Gland-Derived; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases