Proper nervous system function requires the production of diverse cell types in stereotyped positions in the embryonic central nervous system. The long-term objective of this application is to identify within the vertebrate spinal cord. The model system to be studies is the lumbosacral (LS) spinal cord of the avian embryo. During embryogenesis, the avian LS spinal cord acquires characteristic features, including a lateral motor column in which limb motoneuron target identity is distinctive at different axial or anteroposterior levels and a unique pattern of Hoxd-10 expression that varies with axial level. These characteristics become determined at early neural tube stages, that is, the cells of the LS region acquire the ability to proceed along a proper position-specific path of differentiation without further environmental control. A central aim is to identify the source of signals that govern this event. In vivo experiments will address the questions of whether inductive signals are transmitted in a planar manner from posterior to anterior neural regions and whether the remnants of Hensen's node and the primitive streak (the tailbud) are a source of signals. The cellular contributions of the tailbud to anterior LS regions will be mapped. Proposed studies will also assess the signaling functions of paraxial mesoderm and presumptive limb tissue. Techniques to be used include in vivo surgical manipulation, quail/chick chimera construction, in situ hybridization with RNA probes, and retrograde cell tracing. While regional differences may exist within the early neural tube, it is not known if motoneuron precursors are actually specified with respect to target identity at that time. Quail/chick chimeras and/or chimeras of retrovirally-infected and resistant chick strains will be used to examine the role of floorplate signals and neighbor/neighbor interactions in the specification of target identity after early neural tube stages. Overall, results will proved basic information about how neuronal diversity is obtained and may improve the design of surgical cell replacement therapies.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD025676-07
Application #
2673588
Study Section
Neurology B Subcommittee 2 (NEUB)
Project Start
1989-07-01
Project End
2001-03-31
Budget Start
1998-04-01
Budget End
1999-03-31
Support Year
7
Fiscal Year
1998
Total Cost
Indirect Cost
Name
University of Pittsburgh
Department
Biology
Type
Schools of Medicine
DUNS #
053785812
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Misra, Mala; Sours, Emily; Lance-Jones, Cynthia (2012) Hox transcription factors influence motoneuron identity through the integrated actions of both homeodomain and non-homeodomain regions. Dev Dyn 241:718-31
Misra, Mala; Shah, Veeral; Carpenter, Ellen et al. (2009) Restricted patterns of Hoxd10 and Hoxd11 set segmental differences in motoneuron subtype complement in the lumbosacral spinal cord. Dev Biol 330:54-72
Shah, Veeral; Drill, Emily; Lance-Jones, Cynthia (2004) Ectopic expression of Hoxd10 in thoracic spinal segments induces motoneurons with a lumbosacral molecular profile and axon projections to the limb. Dev Dyn 231:43-56
Omelchenko, Natalia; Lance-Jones, Cynthia (2003) Programming neural Hoxd10: in vivo evidence that early node-associated signals predominate over paraxial mesoderm signals at posterior spinal levels. Dev Biol 261:99-115
Lance-Jones, C; Omelchenko, N; Bailis, A et al. (2001) Hoxd10 induction and regionalization in the developing lumbosacral spinal cord. Development 128:2255-68
Lin, J H; Saito, T; Anderson, D J et al. (1998) Functionally related motor neuron pool and muscle sensory afferent subtypes defined by coordinate ETS gene expression. Cell 95:393-407
Matise, M P; Lance-Jones, C (1996) A critical period for the specification of motor pools in the chick lumbosacral spinal cord. Development 122:659-69
Van Swearingen, J; Lance-Jones, C (1995) Slow and fast muscle fibers are preferentially derived from myoblasts migrating into the chick limb bud at different developmental times. Dev Biol 170:321-37
VanSwearingen, J M; Lance-Jones, C (1993) Spatial and temporal patterns of muscle formation in the limb of the avian embryo. Prog Clin Biol Res 383B:553-62
Lance-Jones, C; Dias, M (1991) The influence of presumptive limb connective tissue on motoneuron axon guidance. Dev Biol 143:93-110