The zebrafish glypican knypek controls cell polarity during gastrulation movements of convergent extension.
Mutations in the zebrafish knypek locus impair gastrulation movements of convergent extension that narrow embryonic body and elongate it from head to tail. We demonstrate that knypek regulates cellular movements but not cell fate specification. Convergent extension movement defects in knypek are associated with abnormal cell polarity, as mutant cells fail to elongate and align medio-laterally. Positional cloning reveals that knypek encodes a member of the glypican family of heparan sulfate proteoglycans. Double mutant and overexpression analyses show that Knypek potentiates Wnt11 signaling, mediating convergent extension. These studies provide experimental and genetic evidence that glypican Knypek acts during vertebrate gastrulation as a positive modulator of noncanonical Wnt signaling to establish polarized cell behaviors underlying convergent extension movements.
Topczewski
J
J
Department of Biological Sciences, Vanderbilt University, Nashville, Tennessee 37235, USA.
Sepich
D S
DS
Myers
D C
DC
Walker
C
C
Amores
A
A
Lele
Z
Z
Hammerschmidt
M
M
Postlethwait
J
J
Solnica-Krezel
L
L
D000595:Amino Acid Sequence; D000818:Animals; D019521:Body Patterning; D002455:Cell Division; D003001:Cloning, Molecular; D003545:Cysteine / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D005775:Gastrula / Q000502:physiology*; D006023:Glycoproteins / Q000378:metabolism; D019812:Heparan Sulfate Proteoglycans / Q000235:genetics* / Q000502:physiology*; D017403:In Situ Hybridization; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D013997:Time Factors; D051153:Wnt Proteins; D015027:Zebrafish; D029961:Zebrafish Proteins
D006023:Glycoproteins; D019812:Heparan Sulfate Proteoglycans; D012333:RNA, Messenger; D051153:Wnt Proteins; C092568:Wnt11 protein, zebrafish; D029961:Zebrafish Proteins; C440207:gpc4 protein, zebrafish; D012313:RNA; D003545:Cysteine