Cellular differentiation and control of cell numbers are being investigated in 3 centers of the frog CNS. Similar centers are present in human beings: 1) The lumbar lateral motor column (LMC), whose cells provide motor innervation to hind limb muscles. About 80% of the cells die during larval life. Since cell production and cell death periods overlap extensively, and both processes and cell differentiation are influenced by thyroid hormones, and by environmental factors, thyroid hormone concentrations in """"""""normal"""""""" and hypophysectomized tadpoles are being manipulated, along with changes in temperature, with limb amputation and regeneration, and sciatic nerve transection. LMC cell numbers and degree of differentiation are influenced, and distribution of LMC cells for given control and regenerated muscle, is being studied with HRP intramuscular labelling. Further, how do times of LMC cell formation correlate with times of cell death? 2) The optic tectum. Now it is known when its 1,000,000 cells are produced and when at least 350,000 die. When does cell death stop (up to the 4th postmetamorphic week?)? Why then, and not earlier, particularly after one eye is removed? How does eye removal affect distad interlaminar cell migration? For given tectal areas, what fraction of the final cell population is produced in given larval stages? Over what larval stages can significant replacement of the tectum occur, following partial ablation, and how is this restoration affected by absence of an eye? 3) The mesencephalic fifth nucleus cells. These primary intracentral proprioceptors of the jaw muscles have about 45% of their cells dying at the end of the larval period. To what extent are both cell death and cell growth dependent directly or indirectly on thyroid hormone titer (to be tested with local thyroid hormone pellets)? When are the cells produced? Since only 50% of the cell number is present in hypophysectomized tadpoles, is the last part of cell production hormone-dependent? Is cell death due to a single triggering event, or to multiple or/and prolonged controls? Finally, for all of these (and perhaps related) systems, can a monoclonal antibody be produced which recognizes dying, or prospectively dying, neurons?

Project Start
Project End
Budget Start
Budget End
Support Year
14
Fiscal Year
1992
Total Cost
Indirect Cost
Name
University of Iowa
Department
Type
DUNS #
041294109
City
Iowa City
State
IA
Country
United States
Zip Code
52242