This proposal will study the restriction of developmental potential in the neural crest cells that form the enteric nervous system. This large and most complex division of the peripheral nervous system is derived from a small number of precursor cells that migrate along defined pathways from the vagal crest of the head and the sacral crest of the pelvis. Experiments done with previous support, in which pieces of quail gut were transplanted into appropriate or inappropriate crest migration pathways of younger chick hosts, revealed that those crest-derived cells that first colonize the gut retain a developmental potential that is greater than that which is ultimately exhibited by these cells when they differentiate within the gut. Targets reached by these transplanted cells were appropriate for the sites in which the enteric grafts were placed, and did not reflect the cell's previous history. The proposed experiments will further characterize the developmental potential of these cells by purifying them via immunoselection using a neural-crest specific antibody (NC-1) linked to magnetic beads. Experiments, which transplant these purified cells back into younger host embryos and grow them in culture, will determine: 1) whether the properties of these cells are equivalent to those that migrate out of intact gut segments; how their developmental potential changes as a function of age and of their extent of migration; and 3) whether the developmental potential of the vagal crest-derived cells is different from that of sacral crest-derived cells.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD020470-06
Application #
3318584
Study Section
Neurology B Subcommittee 2 (NEUB)
Project Start
1987-03-01
Project End
1996-02-28
Budget Start
1992-03-01
Budget End
1993-02-28
Support Year
6
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Columbia University (N.Y.)
Department
Type
Schools of Medicine
DUNS #
064931884
City
New York
State
NY
Country
United States
Zip Code
10027
Chalazonitis, A; Tennyson, V M; Kibbey, M C et al. (1997) The alpha1 subunit of laminin-1 promotes the development of neurons by interacting with LBP110 expressed by neural crest-derived cells immunoselected from the fetal mouse gut. J Neurobiol 33:118-38
Chalazonitis, A; Rothman, T P; Chen, J et al. (1994) Neurotrophin-3 induces neural crest-derived cells from fetal rat gut to develop in vitro as neurons or glia. J Neurosci 14:6571-84
Pomeranz, H D; Rothman, T P; Chalazonitis, A et al. (1993) Neural crest-derived cells isolated from the gut by immunoselection develop neuronal and glial phenotypes when cultured on laminin. Dev Biol 156:341-61
Gershon, M D; Chalazonitis, A; Rothman, T P (1993) From neural crest to bowel: development of the enteric nervous system. J Neurobiol 24:199-214
Rothman, T P; Goldowitz, D; Gershon, M D (1993) Inhibition of migration of neural crest-derived cells by the abnormal mesenchyme of the presumptive aganglionic bowel of ls/ls mice: analysis with aggregation and interspecies chimeras. Dev Biol 159:559-73
Rothman, T P; Le Douarin, N M; Fontaine-Perus, J C et al. (1993) Colonization of the bowel by neural crest-derived cells re-migrating from foregut backtransplanted to vagal or sacral regions of host embryos. Dev Dyn 196:217-33
Pomeranz, H D; Rothman, T P; Gershon, M D (1991) Colonization of the post-umbilical bowel by cells derived from the sacral neural crest: direct tracing of cell migration using an intercalating probe and a replication-deficient retrovirus. Development 111:647-55
Rothman, T P; Le Douarin, N M; Fontaine-Perus, J C et al. (1990) Developmental potential of neural crest-derived cells migrating from segments of developing quail bowel back-grafted into younger chick host embryos. Development 109:411-23
Fontaine-Perus, J C; Chanconie, M; Le Douarin, N M et al. (1989) Mitogenic effect of muscle on the neuroepithelium of the developing spinal cord. Development 107:413-22
Rothman, T P; Gershon, M D; Fontaine-Perus, J C et al. (1987) The effect of back-transplants of the embryonic gut wall on growth of the neural tube. Dev Biol 124:331-46