The problem of cell lineage -- how a single
fertilized egg cell undergoes a complex pattern of cell divisions
to generate a multiplicity of distinct cell types -- has been a long-term
interest of our laboratory. We have identified hundreds of mutations
that affect the nearly invariant and completely described C. elegans
cell lineage. Many of the genes defined by these mutations function
in generating cell diversity during development. For example, some
genes act to make the two daughter cells generated by a single cell
division different from each other. Others control spatial patterning.
Many genes that control the C. elegans cell lineage encode
proteins similar to known transcription factors (e.g., unc-86
and lin-11, founding members of the POU and LIM protein families,
respectively), and our studies indicate that the generation of cell
diversity during development is in part regulated by a cascade of
interacting transcription factors.
One of the first cell lineage mutants we characterized defined the
gene lin-4. This gene was the founding member of a set of genes
that control aspects of developmental timing. Since mutations in these
genes cause temporal transformations in cell fates, we named these
genes "heterochronic." The heterochronic gene we discovered
most recently was let-7, which we identified in our studies
of mutants abnormal in the development of the serotonergic HSN neurons,
which drive egg laying. lin-4 and let-7 do not encode
proteins but rather encode small 21-22 nt RNAs, termed micro RNAs,
and act by binding the mRNAs of target genes and preventing translation.
We have recently embarked upon a collaborative project with MIT colleague
David Bartel and our ex-postdoctoral fellow Victor Ambros to characterize
the complete set of more than 100 MICRO
RNAs in the C. elegans genome.
We are currently analyzing the genetic control of the fate of a specific
neuron type, the CEM. The four male-specific CEM neurons, which are
suspected to help the male chemotax toward hermaphrodites, are generated
in both males and hermaphrodites but undergo programmed cell death
in hermaphrodites. We are isolating and characterizing mutants in
which the CEMs fail to die in hermaphrodites and in this way are defining
genes that control both the specification of CEM cell fate and the
decision between survival and the alternative fate of PROGRAMMED
CELL DEATH (APOPTOSIS).
Publications:
Cell Lineage and Cell Fate
Abstracts:
Cell Lineage and Cell Fate
