Natural Science Forum / Biology / Biology / October 2007

hi,

the following is an abstract taken from pubmed. i would like it
clarified wether hdkk1 deletion/suppresion inhibits head development
in xenopus. also, wether hdkk1 plays a similar role in human head
induction.

thanks.

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Functional and structural diversity of the human Dickkopf gene family.

Krupnik VE, Sharp JD, Jiang C, Robison K, Chickering TW, Amaravadi L,
Brown DE, Guyot D, Mays G, Leiby K, Chang B, Duong T, Goodearl AD,
Gearing DP, Sokol SY, McCarthy SA.

Department of Microbiology and Molecular Genetics, Harvard Medical
School and Division of Molecular Medicine, Beth Israel Deaconess
Medical Center, Boston, MA 02215, USA.

Wnt proteins influence many aspects of embryonic development, and
their activity is regulated by several secreted antagonists, including
the Xenopus Dickkopf-1 (xDkk-1) protein. xDkk-1 inhibits Wnt
activities in Xenopus embryos and may play a role in induction of head
structures. Here, we characterize a family of human Dkk-related genes
composed of Dkk-1, Dkk-2, Dkk-3, and Dkk-4, together with a unique
Dkk-3 related protein termed Soggy (Sgy). hDkks 1-4 contain two
distinct cysteine-rich domains in which the positions of 10 cysteine
residues are highly conserved between family members. Sgy is a novel
secreted protein related to Dkk-3 but which lacks the cysteine-rich
domains. Members of the Dkk-related family display unique patterns of
mRNA expression in human and mouse tissues, and are secreted when
expressed in 293T cells. Furthermore, secreted hDkk-2 and hDkk-4
undergo proteolytic processing which results in cleavage of the second
cysteine-rich domain from the full-length protein. Members of the
human Dkk-related family differ not only in their structures and
expression patterns, but also in their abilities to inhibit Wnt
signaling. hDkk-1 and hDkk-4, but not hDkk-2, hDkk-3 or Sgy, suppress
Wnt-induced secondary axis induction in Xenopus embryos. hDkk-1 and
hDkk-4 do not block axis induction triggered either by Xenopus
Dishevelled (Xdsh) or Xenopus Frizzled-8 (Xfz8), both of which
function to transduce signals from Wnt ligands. Thus, hDkks 1 and 4
may inhibit Wnt activity by a mechanism upstream of Frizzled. Our
findings highlight the structural and functional heterogeneity of
human Dkk-related proteins.

PMID: 10570958 [PubMed - indexed for MEDLINE]