Wnt Signaling Pathway.pdf

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Wnt Signaling Pathway
What is Wnt?
The term “Wnt” is derived from the terms wingless and int. The Int oncogenes,
including Int1, were first identified in the mouse mammary tumor. In 1987,
investigators sequenced wingless in Drosophila and found it was the homolog of int-1.
Thus, the int/Wingless family became the Wnt family and int1 became Wnt1. The
name Wnt is a portmanteau of int and Wg and stands for "Wingless-related integration
site". Wnts are secreted factors that regulate cell growth, motility,and di erentiation
during embryonic development. Wnts act in a paracrine fashion by activating diverse
signaling cascades inside the target cells.
Wnt gene family
The Wnt family consists of a number of highly conserved genes that regulate gene
expression, cell behavior,cell adhesion, and cell polarity,including 19 genes in humans
and mice, 7 in Drosophila, and 5 in C. elegans. Wnt-1 is one member of a gene family
whose additional members were isolated either as a target for MMTV insertion (Wnt-3,
Wnt-3A was subsequently isolated by homology to Wnt-3), fortuitously from a
chromosomal walk directed around the cystic fibrosis gene (Wnt-2), or from mouse
embryo RNA using the polymerase chain reaction (Wnt-4, -5A, -5B, -6, -7A,and -7B) .
There are now at least 10 known membersof the Wnt family in the mouse; all of which
are expressed during development, many in the developing nervous system with some
expressed in adult brain as well. In addition, five members of the Wnt family are
expressed in the normal mammary gland in the mouse and are differentially regulated
during pregnancy and lactation. This family has been remarkably well conserved
throughout evolution, with homologues present in both invertebrates and vertebrates.
In addition to the predicted amino acid sequence similarities among family members, a
role in cell signaling has also been documented for several Wnt family members. For
example, wingless, the Drosophila homologue of Wnt-1, is necessary for proper
segmental patterning of the embryo and is proposed to function locally via cell-cell