Postmigratory enteric and sympathetic neural precursors share common, developmentally regulated, responses to BMP2.
The development of enteric and sympathetic neurons from neural crest precursor cells is regulated by signals produced by the embryonic environments to which the cells migrate. Bone morphogenetic proteins (BMPs) are present in the developing embryo and act to induce neuronal differentiation and noradrenergic properties of neural crest cells. We have investigated the role of BMP2 in regulating the appearance of distinct populations of autonomic neurons from postmigratory, HNK-1-positive neural crest precursor cells. BMP2 promotes neuronal differentiation of sympathetic and enteric precursor cells isolated from E14.5 rat. The effects of BMP2 change over time, resulting in a decrease in neuron number that can be attributed to apoptotic cell death. BMP2-dependent neuron death is rescued by gut-derived factors that provide trophic support to maturing neurons, indicating that BMP2 regulates the acquisition of trophic dependence of developing peripheral neurons. In addition to regulating neuron number, BMP2 promotes both panneuronal maturation and the acquisition of an enteric phenotype, as measured by lineage-specific changes in the expression of tyrosine hydroxylase and MASH-1. While BMP2 is sufficient to induce neuronal differentiation and panneuronal development, these results suggest that additional factors in the environment must collaborate with BMP2 to promote the final noradrenergic phenotype of sympathetic neurons.
Pisano
J M
JM
Department of Biology, Volen National Center for Complex Systems, Brandeis University, 415 South Street, Waltham, Massachusetts, 02454, USA.
Colón-Hastings
F
F
Birren
S J
SJ
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D051792:Basic Helix-Loop-Helix Proteins; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology*; D002452:Cell Count; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D019070:Cell Lineage / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000378:metabolism; D017615:Enteric Nervous System / Q000166:cytology / Q000187:drug effects* / Q000196:embryology / Q000201:enzymology; D007150:Immunohistochemistry; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009432:Neural Crest / Q000166:cytology / Q000187:drug effects* / Q000196:embryology / Q000201:enzymology; D016900:Neurofilament Proteins / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D051381:Rats; D011919:Rats, Inbred Strains; D013234:Stem Cells / Q000187:drug effects*; D013564:Sympathetic Nervous System / Q000166:cytology / Q000187:drug effects* / Q000196:embryology / Q000201:enzymology; D014157:Transcription Factors / Q000378:metabolism; D016212:Transforming Growth Factor beta
D051792:Basic Helix-Loop-Helix Proteins; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D017077:Culture Media, Conditioned; D004268:DNA-Binding Proteins; D009419:Nerve Tissue Proteins; D016900:Neurofilament Proteins; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; C499318:Ascl1 protein, rat; C525720:Bmp2 protein, rat