Effects of NGF, NT-3 and GDNF family members on neurite outgrowth and migration from pelvic ganglia from embryonic and newborn mice

Ashley L Stewart,Kazuto Kobayashi,Heather M Young,Richard B Anderson

doi:10.1186/1471-213x-8-73

Ashley L Stewart, Kazuto Kobayashi + Show 2 more

Open Access

https://doi.org/10.1186/1471-213x-8-73

Copy DOI

Abstract

BackgroundPelvic ganglia are derived from the sacral neural crest and contain both sympathetic and parasympathetic neurons. Various members of the neurotrophin and GDNF families of neurotrophic factors have been shown to play important roles in the development of a variety of peripheral sympathetic and parasympathetic neurons; however, to date, the role of these factors in the development of pelvic ganglia has been limited to postnatal and older ages. We examined the effects of NGF, NT-3, GDNF, neurturin and artemin on cell migration and neurite outgrowth from explants of the pelvic ganglia from embryonic and newborn mice grown on collagen gels, and correlated the responses with the immunohistochemical localization of the relevant receptors in fixed tissue.ResultsCell migration assays showed that GDNF strongly stimulated migration of tyrosine hydroxylase (TH) cells of pelvic ganglia from E11.5, E14.5 and P0 mice. Other factors also promoted TH cell migration, although to a lesser extent and only at discrete developmental stages. The cells and neurites of the pelvic ganglia were responsive to each of the GDNF family ligands – GDNF, neurturin and artemin – from E11.5 onwards. In contrast, NGF and NT-3 did not elicit a significant neurite outgrowth effect until E14.5 onwards. Artemin and NGF promoted significant outgrowth of sympathetic (TH+) neurites only, whereas neurturin affected primarily parasympathetic (TH-negative) neurite outgrowth, and GDNF and NT-3 enhanced both sympathetic and parasympathetic neurite outgrowth. In comparison, collagen gel assays using gut explants from E11.5 and E14.5 mice showed neurite outgrowth only in response to GDNF at E11.5 and to neurturin only in E14.5 mice.ConclusionOur data show that there are both age-dependent and neuron type-dependent differences in the responsiveness of embryonic and neo-natal pelvic ganglion neurons to growth factors.

Highlights

Pelvic ganglia are derived from the sacral neural crest and contain both sympathetic and parasympathetic neurons
We report the effects of neurotrophin and glial cell line-derived neurotrophic factor (GDNF) family ligands (GFLs) signalling on cell migration and neurite outgrowth of parasympathetic and sympathetic neurons in pelvic ganglia from embryonic and newborn mice and correlate the responses with the expression of the corresponding receptors
Response of pelvic plexus neurons to neurotrophic factors Explants of E11.5 or E14.5 pelvic plexus primordium or P0 pelvic ganglia were grown on collagen gels, with or without 40 ng/ml NT-3, or 100 ng/ml GDNF, artemin, neurturin or nerve growth factor (NGF)

Summary

Introduction

Pelvic ganglia are derived from the sacral neural crest and contain both sympathetic and parasympathetic neurons. The pelvic ganglia are comprised of a mixture of sympathetic and parasympathetic post-ganglionic neurons [1,2,10]. Both sympathetic and parasympathetic post-ganglionic neurons of pelvic ganglia are derived from the sacral neural crest [11,12,13,14]. Sacral neural crest cells migrate ventrally and coalesce into aggregates between the distal hindgut and the urogenital sinus [11,15]. Some sacral neural crest cells contribute neurons and glial cells to distal regions of the gut [12]; these cells reside transiently within the pelvic plexus primordia for around 3 days before entering the hindgut [11,15,16,17]

Methods

Results

Discussion

Conclusion