title: Vascularisation is not necessary for gut colonisation by enteric neural crest cells.
abstract: The vasculature and nervous system share striking similarities in their networked, tree-like architecture and in the way they are super-imposed in mature organs. It has previously been suggested that the intestinal microvasculature network directs the migration of enteric neural crest cells (ENCC) along the gut to promote the formation of the enteric nervous system (ENS). To investigate the inter-relationship of migrating ENCC, ENS formation and gut vascular development we combined fate-mapping of ENCC with immunolabelling and intravascular dye injection to visualise nascent blood vessel networks. We found that the enteric and vascular networks initially had very distinct patterns of development. In the foregut, ENCC migrated through areas devoid of established vascular networks. In vessel-rich areas, such as the midgut and hindgut, the distribution of migrating ENCC did not support the idea that these cells followed a pre-established vascular network. Moreover, when gut vascular development was impaired, either genetically in Vegfa(120/120) or Tie2-Cre;Nrp1(fl/-) mice or using an in vitro Wnt1-Cre;Rosa26(Yfp/+) mouse model of ENS development, ENCC still colonised the entire length of the gut, including the terminal hindgut. These results demonstrate that blood vessel networks are not necessary to guide migrating ENCC during ENS development. Conversely, in miRet(51) mice, which lack ENS in the hindgut, the vascular network in this region appeared to be normal suggesting that in early development both networks form independently of each other.
authors.affiliation: Neural Development Unit, UCL Institute of Child Health, 30 Guilford Street, London WC1N 1EH, United Kingdom.
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Delalande
authors.affiliation: Neural Development Unit, UCL Institute of Child Health, 30 Guilford Street, London WC1N 1EH, United Kingdom.
authors.forename: Dipa
authors.initials: D
authors.lastname: Natarajan
authors.affiliation: Neural Development Unit, UCL Institute of Child Health, 30 Guilford Street, London WC1N 1EH, United Kingdom.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Vernay
authors.affiliation: UCL Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, United Kingdom.
authors.forename: Malcolm
authors.initials: M
authors.lastname: Finlay
authors.affiliation: UCL Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, United Kingdom.
authors.forename: Christiana
authors.initials: C
authors.lastname: Ruhrberg
authors.affiliation: Neural Development Unit, UCL Institute of Child Health, 30 Guilford Street, London WC1N 1EH, United Kingdom.
authors.forename: Nikhil
authors.initials: N
authors.lastname: Thapar
authors.affiliation: Neural Development Unit, UCL Institute of Child Health, 30 Guilford Street, London WC1N 1EH, United Kingdom; Department of Clinical Genetics, The Erasmus University Medical Center, Rotterdam, The Netherlands. Electronic address: alan.burns@ucl.ac.uk.
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Burns
mesh_terms: D000818:Animals; D017615:Enteric Nervous System / Q000502:physiology*; D007422:Intestines / Q000098:blood supply / Q000166:cytology*; D051379:Mice; D018919:Neovascularization, Physiologic; D009432:Neural Crest / Q000166:cytology*
keywords: Blood vessels; Enteric nervous system; Migration; Neural crest cells; Vascular system