A central question of developmental neurobiology is how the descendants of an apparently homogeneous neuroepithelium give rise to the beutiful and complex patterns observed in the mature nervous system. Cell migration of cell lineage are two major processes involved in the formation of proper neuronal patterning. Because these patterns play an important role in the functioning of neuronal systems, a knowledge of their genesis is central to an understanding of neuronal function. The long term goals of these experiments is to employ newly developed techniques to follow neuronal migration and cell lineage in the vertebrate nervous system. These techniques permit single neuroblasts to be uniquely labeled in the intact embryo. The goal of the proposed experiments is to explore cell lineages and movements in the vertebrate hindbrain, which is subdivided into a series of metameric epithelial units termed rhombomerases. In the chicken embryo, the rhombomeres first become apparent on the secon day of development as a periodic pattern of ridges dividing the hindbrain rudiment into seven rostrocaudal segments. The segmental pattern is reflected in the pattern of neurogenesis, with even-numbered segments developing recognizable neurons before the odd-numbered segments. The proposed experiments will explore the functional consequences of the rhombomers by performing a prospective lineage analysis of neural tube cells using microinjected cell autonomous vital dyes. Only the descendants of the injected cell, which inherit the dye at mitosis, will be labeled. By analyzing the phenotypes of the labeled descendants of a single precursor, a direct analysis of cell lineage is possible. Furthermore, because the vital dye can be observed in the living intact embryo, comparison of the position of the original dye-injected cell and the eventual positions of its progeny offer a direct measure of cell migration of cell mixing. In particular, the experiments will determine: 1. The spatial patterns of neurogenesis in the developing hindbrain, directly assessing if the populations of cells comprising individual rhombomeres are segregated by lineage restriction boundaries. 2. The phenotypes of the descendants of the labeled precursors in the hindbrain to determine if the apparent early seeregation of the hindbrain is also manifest in an early segregation of cell fate. 3. The spatial patterns and fates of the descendants of single neural tube cells in the trunk region of the embryo to determine if there is a parallel of the neuroblasts even at spinal levels of the neuroaxis, where there are no noticeable boundaries.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD029304-02
Application #
3330781
Study Section
Neurology B Subcommittee 2 (NEUB)
Project Start
1991-09-01
Project End
1994-08-31
Budget Start
1992-09-01
Budget End
1993-08-31
Support Year
2
Fiscal Year
1992
Total Cost
Indirect Cost
Name
California Institute of Technology
Department
Type
Schools of Arts and Sciences
DUNS #
078731668
City
Pasadena
State
CA
Country
United States
Zip Code
91125
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Scherson, T; Serbedzija, G; Fraser, S et al. (1993) Regulative capacity of the cranial neural tube to form neural crest. Development 118:1049-62
Zimmerman, K; Shih, J; Bars, J et al. (1993) XASH-3, a novel Xenopus achaete-scute homolog, provides an early marker of planar neural induction and position along the mediolateral axis of the neural plate. Development 119:221-32