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FRISC: The Faculty Research Interests Science Comparator |
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Assistant Professor of Pediatrics
Genetics and
Development
Office: (214) 648-3383
FAX: (214) 648-1488
Email: scott.cameron@utsouthwestern.edu
Developmental biology is defined by the attempt to understand
how different cell fates are established in a multicellular organism. Mutations
in this process contribute to disease in people. Caenorhabditis elegans
offers extraordinarily powerful tools for the identification and analysis of
pathways that regulate cell fates, including sophisticated genetics and a known,
invariant cell lineage (i.e. the ancestry and fate of every cell is known from
the zygote to the adult in a wild type animal). Knowledge of the invariant cell
lineage makes it possible to identify and study mutations affecting cell fates
at the level of individual cells. My laboratory focuses on how the pattern of
cell fates is determined in one tissue of C. elegans, the ventral nerve
cord. In this tissue during postembryonic development 65 cells are generated, of
which ten undergo the fate of programmed cell death; the surviving cells survive
and differentiate to become motor neurons of several specific types.
Characterization of three genes identified in genetic screens for mutants with
abnormal patterns of programmed cell deaths and motor neuron fates in the
ventral cord indicate that each gene contributes to the pattern of cell fates
and cell deaths in a different way- one by determining neuroblast fate, a second
by acting in differentiating neurons to specify neuronal fate and prevent cell
death, and a third by providing spatial information to the developing ventral
cord.
Mutations of one gene, pag-3, in C. elegans result in a
specific defect in the cell lineages of ventral cord neuroblasts. We have
knocked out the mouse homologues of pag-3 and found that the mice have defects
in the hematopoietic lineages precisely consistent with what was predicted based
on the phenotype of the C. elegans mutants. The defects in the
hematopoietic cells occur very early during the commitment to the hematopoietic
lineages, suggesting that these genes may be part of a mechanism controlling
development of the hematopoietic stem cells. Several of the other genes we
identified as affecting development of the ventral nerve cord have mammalian
homologue(s) that also function in hematopoietic cells, and two can cause
hematopoietic cancers when mutated, although how these factors contribute to
malignancy is unclear. We intend to define precisely how each of the genes
functions during ventral cord development in C. elegans and then to use
these findings to develop specific hypotheses for how the mammalian homologues
function during hematopoiesis and the development of hematopoietic cancers.
Selected Publications:
Saleque, S., Cameron, S. and Orkin, S.H. (2002). The zinc-finger
protooncogene Gfi-1b is essential for development of the erythroid and
megakaryocytic lineages. Genes and Development, in press.
Cameron, S., Clark, S., McDermott, J.B., Aamodt, E. and Horvitz,
H.R. (2002). PAG-3, a Zn finger transcription factor, determines neuroblast fate
in C. elegans. Development, in press.
Reddien, P.W., Cameron, S. and Horvitz, H.R. (2001).
Phagocytosis promotes programmed cell death in C. elegans. Nature 412:
198-202.
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Last updated: 20 Feb 2002
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