Abstract of Thesis

In both Drosophila and Schistocerca, a ganglion mother cell (GMC) divides to produce two sibling neurons, which often acquire different fates ('A'/'B'). In Drosophila, in the absence of either the Notch receptor or the Delta ligand, both siblings adopt the 'B' fate. It is shown here that the intrinsic determinant Numb is also required in Drosophila sibling neurons; both siblings acquire the 'A' fate in numb germline mutants. In Drosophila regulator of cyclin A (rca1) mutants, many GMCs fail to divide; these GMCs differentiate in the manner of one sibling neuron ('B'). In rca1, numb mutants, cell fate alterations ('B' to 'A') in the absence of a true sibling. Additionally, Delta provided from the mesoderm is sufficient to allow sibling neurons to acquire differential fates, suggesting that this signal can be received from outside the sibling cells.

I have isolated fragments of numb and Delta homologues from Schistocerca americana. Schistocerca numb transcript is expressed broadly throughout the embryo during neural development. Schistocerca Delta transcript is expressed in a dynamic pattern during embryogenesis that is quite different from Delta expression in Drosophila. Schistocerca Delta expression is observed in delaminated neuroblasts but not in the neuroectoderm, suggesting that Delta may act in neuroblasts to inhibit neuroectodermal cells from adopting neural fates. Schistocerca Delta is also expressed transiently in sibling neuron pairs throughout neurogenesis, but not in the mesoderm adjacent to these cells. This suggest that Notch-Delta signaling may occur between sibling neurons in Schistocerca. These data indicate that CNS cell fate determination mechanisms may be quite different between Drosophila and grasshopper.

Education:

1995 to 2001

University of Chicago	
Dept. of Molecular Genetics and Cell Biology

1991 - 1995

University of California at Los Angeles, 
B.S., Microbiology and Molecular Genetics
B.S., Anthropology, Specialization in Computing

Publications and Presentations:

Lear, B.C., J.B. Skeath, and N.H. Patel (1999). Neural cell fate in rca1 and cycA mutants: the roles of intrinsic and extrinsic factors in asymmetric division in the Drosophila central nervous system. Mech. Dev. 88: 207-219.

Meetings Attended:

Lear, B.C., J.B. Skeath, and N.H. Patel. Cell fate determination mechanisms in the insect central nervous system, Poster 191, Society for Developmental Biology annual meeting, Boulder, CO, 2000.

Lear, B.C. and N.H. Patel. "Cell fate determination between sibling neurons." (Abstract) Annual Conference of Drosophila Research, 1997, 195C.

Lear, B.C. and N.H. Patel. "Cell fate determination between sibling neurons." (Abstract) Annual Conference of Drosophila Research, 1998, 546A.

Research Interests:

My research in the Patel lab involves the question of how neural cell fates are specified during insect development.  I have focused my studies on the embryonic central nervous system (CNS) of the insects Drosophila melanogaster and Schistocerca americana (grasshopper). There are many developmental similarities in the CNS of these two species, resulting in similar patterns of neurons. For example, in both species, the division of ganglion mother cell (GMC) 1-1a generates the sibling neurons aCC and pCC. This division is of particular interest to me because the sibling cells aCC and pCC acquire very different fates in the CNS; moreover, the process of cell fate determination of the aCC and pCC siblings has been studied in both species, and there are some potentially interesting differences in the processes between these two species.

In the grasshopper, ablation of either aCC or pCC immediately after GMC division results in the remaining cell taking the fate of pCC. However, when 1-2% of development is allowed to proceed between the GMC division and cell ablation, the remaining cell acquires the fate of aCC or pCC equally (Kuwada and Goodman, 1985). This experiment suggests that interactions between the sibling cells are important to this cell fate decision, and that, in the absence of these interactions, the cell would acquire the pCC fate. In Drosophila melanogaster, it has been determined that both extrinsic (Notch /Delta) and intrinsic (Numb) factors are absolutely required for the aCC/pCC siblings to acquire differential fates. In the absence of the extracellular signaling components Notch or Delta, both siblings acquire the aCC fate (Skeath and Doe, 1998); in the absence of maternal and zygotic contribution of the intrinsic factor Numb, both siblings acquire the pCC fate (Lear, Skeath, and Patel, 1999). Moreover, our data indicate that extracellular interactions do not need to occur between sibling neurons in order for the cells to acquire different fates (see Lear et al., 1999). Currently, I am using various methodologies to further analyze aCC/pCC fate decisions in the grasshopper. Despite the fact that the steps of neural development look similar between Drosophila and Schistocerca, the mechanisms of sibling neuron fate determination may actually be quite different.