The long-term goals of this project are to identify and characterize the trophic requirements of sub-populations of developing spinal motoneurons (MNs) in the chick embryo. The central hypothesis to be tested is that MNs require distinct target-derived trophic agents for their survival depending upon their peripheral targets. For example, cranial MNs or MNs in non-limb innervating regions of the spinal cord may require different trophic factors from MNs that innervate limb muscles; or, within limb-innervating regions, MNs may differ depending on whether they innervate slow vs. fast or flexor vs. extensor muscles. To begin to test this hypothesis the investigator will determine if: (1) MNs express different patterns of trophic factor receptors depending upon their location, synaptic targets or stage of development; (2) neurotrophic factors are differentially expressed in muscle sub-types (fast vs. slow) or in muscles in different regions (e.g. limb vs. non-limb); and (3) Trophic agents administered alone or in combinations selectively promote the survival of MN subtypes and in vivo based on the receptor or ligand expression patterns of MNs identified in aims 1 and 2. The proposed studies are the first systematic attempt to examine the question of whether MNs differ in their trophic requirements during development according to their location, synaptic targets or stage of maturation. In addition to being important for furthering our basic understanding of MN development, the new information generated could potentially be used to devise more rationale of therapeutic strategies for the use of neurotrophic factors in the treatment of MN and other neurodegenerative diseases.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
3R01NS020402-20S1
Application #
6751408
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Leblanc, Gabrielle G
Project Start
1983-06-01
Project End
2003-08-31
Budget Start
2002-09-01
Budget End
2003-08-31
Support Year
20
Fiscal Year
2003
Total Cost
$30,000
Indirect Cost
Name
Wake Forest University Health Sciences
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
937727907
City
Winston-Salem
State
NC
Country
United States
Zip Code
27157
Kim, Woon Ryoung; Chun, Sung Kun; Kim, Tae Woo et al. (2011) Evidence for the spontaneous production but massive programmed cell death of new neurons in the subcallosal zone of the postnatal mouse brain. Eur J Neurosci 33:599-611
Kim, Woon Ryoung; Park, Ok-Hee; Choi, Sukwoo et al. (2009) The maintenance of specific aspects of neuronal function and behavior is dependent on programmed cell death of adult-generated neurons in the dentate gyrus. Eur J Neurosci 29:1408-21
Oppenheim, Ronald W; Blomgren, Klas; Ethell, Douglas W et al. (2008) Developing postmitotic mammalian neurons in vivo lacking Apaf-1 undergo programmed cell death by a caspase-independent, nonapoptotic pathway involving autophagy. J Neurosci 28:1490-7
Jung, A-Rong; Kim, Tae Woo; Rhyu, Im Joo et al. (2008) Misplacement of Purkinje cells during postnatal development in Bax knock-out mice: a novel role for programmed cell death in the nervous system? J Neurosci 28:2941-8
Kim, Woon Ryoung; Kim, Younghwa; Eun, Bokkee et al. (2007) Impaired migration in the rostral migratory stream but spared olfactory function after the elimination of programmed cell death in Bax knock-out mice. J Neurosci 27:14392-403
Park, Ok-hee; Lee, Kea Joo; Rhyu, Im Joo et al. (2007) Bax-dependent and -independent death of motoneurons after facial nerve injury in adult mice. Eur J Neurosci 26:1421-32
Sato, N; Sakuma, C; Sato, Y et al. (2006) Distinct susceptibility of developing neurons to death following Bax overexpression in the chicken embryo. Cell Death Differ 13:435-45
Winseck, Adam K; Oppenheim, Ronald W (2006) An in vivo analysis of Schwann cell programmed cell death in embryonic mice: the role of axons, glial growth factor, and the pro-apoptotic gene Bax. Eur J Neurosci 24:2105-17
Buss, Robert R; Gould, Thomas W; Ma, Jianjun et al. (2006) Neuromuscular development in the absence of programmed cell death: phenotypic alteration of motoneurons and muscle. J Neurosci 26:13413-27
Sun, Woong; Gould, Thomas W; Newbern, Jason et al. (2005) Phosphorylation of c-Jun in avian and mammalian motoneurons in vivo during programmed cell death: an early reversible event in the apoptotic cascade. J Neurosci 25:5595-603

Showing the most recent 10 out of 109 publications