FRIZZLED RECEPTORS AND EMBRYOGENESIS

Project: Research project

Project Details

Description

Vertebrate embryonic patterning is the process of generating the proper
cellular diversity from a collection of pluripotent cells and involves a
series of sequential cell-cell communication cascades. Several families
of secreted proteins have been identified whose role in development is to
act as signaling molecules in these important communication pathways.
Prominent among these molecular messengers are members of the transforming
growth factor beta (TGF-beta), hedgehog, noggin, and wnt gene families.
To date, receptors have been isolated for the TGF-beta superfamily, with
the identification of the putative receptors for these other three
important signaling molecules yet to be determined. We have characterized
members of the frizzled family of receptor-like molecules from zebrafish
and Xenopus to test whether these genes function in the patterning of the
vertebrate embryo, serving perhaps as a receptor for the wnt gene family
of secreted factors.

We will pursue this set of vertebrate fz gene family members with the
specific goals of:

I. Molecular characterization of three members of the fz gene family
during embryogenesis.

II. Determination of th role of fz genes in embryonic development through
the use of overexpression studies.

III.Investigation of the zygotic fz gene function in zebrafish embryos.

IV. Determination of maternal fz gene function in Xenopus embryos.

V. Identification of the signaling cascade(s) mediated by fz family
members during embryonic development.

We will manipulate specific fz genes in both zebrafish and Xenopus embryos
by microinjection of synthetic transcripts to ectopically overexpress fz
genes during embryogenesis. We will generate zebrafish strains carrying
mutations in fz genes to identify pathways required for zygotic fz gene
function. The generation of Xenopus embryos depleted of a maternally-
expressed fz gene using antisense oligonucleotides will be used to address
the maternal function of fz genes in embryogenesis. Using these tools, we
will identify the signaling cascades mediated by this family of receptor-
like molecules in an attempt to understand in a broader context the role
this new gene family plays in development.
StatusFinished
Effective start/end date9/1/978/31/03

ASJC

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)