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[S2]: Sculpting the sympathetic ganglia: Revealing the interplay of cell movements and molecular signals
Author(s) -
KasemeierKulesa J.C.,
Bradley R.,
Pasquale E.B.,
Lefcort F.,
Kulesa P.M.
Publication year - 2006
Publication title -
international journal of developmental neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.761
H-Index - 88
eISSN - 1873-474X
pISSN - 0736-5748
DOI - 10.1016/j.ijdevneu.2006.09.005
Subject(s) - neuroscience , biology , communication , psychology , cognitive science
BMPs play crucial roles in the determination of the anteroposterior and radial axes of the primordial bowel. In vitro and in vivo approaches have been utilized to test the hypotheses that BMPs2 and 4 continue to act in later development to regulate the differentiation of enteric neurons and glia. The later effects of BMPs were analyzed in culture of post-migratory crest-derived precursors isolated from within the bowel at E12 and later ages by immunoselection with antibodies to p75. Transgenic mice over-expressing BMP4 or its antagonist noggin, under the control of the neuron specific enolase (NSE) promoter, were obtained to increase or interfere with BMP signaling after the gut has become colonized by crest-derived cells. Molecules involved in BMP signaling (BMPs2 and 4, BMPR-II –IA or IB, their downstream effectors) are expressed in enteric crestand non-crest-derived cells throughout the period of gangliogenesis. Because a variety of BMP antagonists are also expressed, BMP signaling must be tightly regulated. By enhancing neuronal differentiation, BMPs oppose the GDNF-induced proliferation of precursors cells and thus, limit expansion of the enteric nervous system (ENS). BMPs also up-regulate TrkC expression and thus promote dependency on NT-3. Because the onset of changes in BMP signaling does not start until NSE expression begins (E14) in the ENS of transgenic mice, neurons that are born early in ontogeny (5-HT, ChAT, calretinin, calbindin) develop in excess or are unchanged. In contrast neurons that arise later (TrkCexpressing, submucosal NOS-, GABA-, dopaminergicand CGRPexpressing) are reduced. At E16 pre-treatment with BMP-4 CNTF, enhances responsiveness to glial growth factor-2/neuregulin-1 by increasing the proportion of GFAPexpressing cells. BMP-4 + CNTF, enhances the proportion of those that co-express ErbB3, the binding receptor subunit for GGF2. These observations support the idea that the BMPs continue to regulate development and growth factor responsiveness of enteric neurons and glia beyond the time of gut formation.