ZFIN ID: ZDB-FIG-130821-5
Anderson et al., 2013 - Hepatocyte Growth Factor Signaling in Intrapancreatic Ductal Cells Drives Pancreatic Morphogenesis. PLoS Genetics   9(7):e1003650 Full text @ PLoS Genet.
ADDITIONAL FIGURES
EXPRESSION / LABELING:
Genes:
Fish:
Knockdown Reagents:
Anatomical Terms:
Stage: Protruding-mouth
PHENOTYPE:
Fish:
Knockdown Reagents:
Observed In:
Stage: Protruding-mouth

Fig. 1

donuts908 is a hypomorphic allele of met.

(A–E) Exocrine pancreas (xp) structure marked by ptf1a:GFP expression in 3 dpf WT (A,D), and in type 1 (B) and type 2 (C,E) donut mutants. The pectoral fins (arrowheads) of donut mutants lack muscle tone, often asymmetrically, leading to their “open wing” appearance (right arrow, E). (F) Penetrance (pen) and expressivity (ex) of the donut phenotype. A small fraction of WT embryos shows donut-like pancreatic phenotypes, while 22% of clutchmates from heterozygous intercrosses exhibited either a spherical (55%) or an intermediately shortened (45%) pancreas. n below bars represents the number of embryos examined from WT clutches (right), heterozygote in-crossed clutches (center), and embryos exhibiting donut-like pancreatic phenotypes (right). (G–I) donut mutants have a lesion in met. donut was mapped to a critical interval on Chr. 25 containing 14 annotated genes (G); met showed a T2324G variant (H) causing an L775R amino acid substitution (I). (J,K) Model structures of the human MET IPT3 domain with isoleucine 777 (analogous to zebrafish residue L775) marked green (J) or substituted arginine marked red (K). (L) Diagram of Met showing the I777R substitution localized to the high affinity HGF binding site in IPT3, and the furin cleavage site in the semaphorin-like domain. (M–P) Morpholino-mediated knockdown of met (M,N) or hgfa/b (O,P) resulted in phenocopy of the donut mutation. (Q) Dose dependence of morpholino-induced phenotypes. At 8 ng, metMO exhibited some non-specific developmental delay, suggesting toxicity. pen, penetrance; ex, expressivity; li, liver; pm, plasma membrane.

Gene Expression Details
Gene Antibody Fish Conditions Stage Anatomy Assay
DsRed gz15Tg; jh1Tg; m1018Tg standard conditions Protruding-mouth liver IFL
gz15Tg; jh1Tg; m1018Tg + MO1-hgfa + MO1-hgfb standard conditions Protruding-mouth liver IFL
gz15Tg; jh1Tg; m1018Tg + MO1-met standard conditions Protruding-mouth liver IFL
mets908/s908; gz15Tg; jh1Tg; m1018Tg standard conditions Protruding-mouth liver IFL
EGFP gz15Tg; jh1Tg; m1018Tg standard conditions Protruding-mouth exocrine pancreas IFL
Protruding-mouth eye IFL
Protruding-mouth hindbrain IFL
gz15Tg; jh1Tg; m1018Tg + MO1-hgfa + MO1-hgfb standard conditions Protruding-mouth exocrine pancreas IFL
Protruding-mouth eye IFL
Protruding-mouth hindbrain IFL
gz15Tg; jh1Tg; m1018Tg + MO1-met standard conditions Protruding-mouth exocrine pancreas IFL
Protruding-mouth eye IFL
Protruding-mouth hindbrain IFL
mets908/s908; gz15Tg; jh1Tg; m1018Tg standard conditions Protruding-mouth exocrine pancreas IFL
Protruding-mouth eye IFL
Protruding-mouth hindbrain IFL
Antibody Labeling Details No data available
Phenotype Details
Fish Conditions Stage Phenotype
gz15Tg; jh1Tg; m1018Tg + MO1-hgfa + MO1-hgfb standard conditions Protruding-mouth liver morphology, abnormal
Protruding-mouth pancreas spheroid, abnormal
gz15Tg; jh1Tg; m1018Tg + MO1-met standard conditions Protruding-mouth pancreas spheroid, abnormal
mets908/s908; gz15Tg; jh1Tg; m1018Tg standard conditions Protruding-mouth pancreas spheroid, abnormal
Protruding-mouth pectoral fin exserted, abnormal
Protruding-mouth pectoral fin increased angle to trunk, abnormal
Protruding-mouth pectoral fin musculature decreased tonicity, abnormal
Acknowledgments:
ZFIN wishes to thank the journal PLoS Genetics for permission to reproduce figures from this article. Please note that this material may be protected by copyright. Full text @ PLoS Genet.