The long range goal of this project is to understand the molecular and cellular mechanisms by which the C. elegans embryo is patterned and the body plan is elaborated under the control of embryonically expressed (zygotic) genes, after maternal gene products have specified early blastomere fates. During the past project period, we have identified and begun to analyze the functions of several genes encoding transcription factors that appear to be important high-level regulators of zygotic posterior patterning control, including the caudal homolog pal-i, two newly discovered Hox posterior-group (AbdB/Hox9-13) homologs, nob-] and php-3, at least one of which we have shown to be essential for embryonic viability, and the homothorax/Meis homolog, unc-62, which we have also shown to be essential. We are now in a position to approach two major unanswered questions of C. elegans embryogenesis: First, how do the maternally expressed genes that dictate earlier cleavage-stage blastomere determination regulate the transition, around the time of gastrulation onset, to zygotically controlled elaboration of the body plan under control of genes like those above? Second, to what extent is later patterning controlled by the lineal programming, characteristic of several aspects of C. elegans development, as opposed to the regional specification of cell fates that is seen in more complex embryos with larger numbers of cells? Our work will also shed light on an evolutionary question: the extent to which the basic functions of these patterning genes are conserved between the cellular embryo of C. elegans and the initially syncytial embryo of Drosophila, where their mechanisms are presently better understood. Our five specific aims for the coming project period will focus on 1) understanding the functions of the posterior group Hox genes nob-I and php-3, 2) determining how these two genes and pal-I, the caudal homolog, are regulated by maternal and other zygotic genes, 3) clarifying the function and regulation of unc-62, the homothorax/Meis ortholog and a likely Hox protein cofactor, 4) characterizing the interactions of these gene products with each other and with other proteins, and 5) identifying downstream regulatory targets of these genes.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD014958-22
Application #
6476683
Study Section
Cell Development and Function Integrated Review Group (CDF)
Program Officer
Klein, Steven
Project Start
1980-12-01
Project End
2005-11-30
Budget Start
2001-12-01
Budget End
2002-11-30
Support Year
22
Fiscal Year
2002
Total Cost
$329,787
Indirect Cost
Name
University of Colorado at Boulder
Department
Biochemistry
Type
Schools of Arts and Sciences
DUNS #
City
Boulder
State
CO
Country
United States
Zip Code
80309
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