hgfa
Danio rerio
Gene Name: hepatocyte growth factor
Aliases: hgf1; si:dkey-146j3.2
Human Ortholog: HGF
Aliases: hgf1; si:dkey-146j3.2
Human Ortholog: HGF
Summary Statistics:
# of Reports: 1
# of Models: 2
# of Reports: 1
# of Models: 2
External Links
Model Summary
Knockdown of hgfa independently did not affect the generation of HuC-GFP-positive neurons, suggesting a redundant role in cerebellar development. Double knockdown of hgfa and hgfb, however, resulted in increased mortality, reduction in the number of newly differentiated cerebellar neurons as well as as granule cell precursors and abnormal dorsal cerebellar folds that are not completely fused. Double hgf morphants also showed decreased expression of ptf1a, rora2, ebf2, pax6a, and reln genes, but no change in expression of olig2, atoh1a, atoh1b, phox2a, or fgf8 genes. Additional changes wer increased cell death and abnormal patterns of facial motor neuron migration.
References
Type
Title
Author, Year
Primary
The autism susceptibility gene met regulates zebrafish cerebellar development and facial motor neuron migration.
Z_HGFA_1_KD_HM_MO
Model Type:
Genetic
Model Genotype: Wild type
Mutation: Embryos were microinjected with 1.5-3nl antisense morpholino oligonucleotides targeting hgfa translation start site and blocking hgfa mRNA splicing at position exon6 - intron6, leading to a truncated hgfa protein.
Allele Type: Loss-of-function
Strain of Origin: Wild-type fish strain *AB
Genetic Background: Not reported
ES Cell Line:
Mutant ES Cell Line:
Model Source:
Model Genotype: Wild type
Mutation: Embryos were microinjected with 1.5-3nl antisense morpholino oligonucleotides targeting hgfa translation start site and blocking hgfa mRNA splicing at position exon6 - intron6, leading to a truncated hgfa protein.
Allele Type: Loss-of-function
Strain of Origin: Wild-type fish strain *AB
Genetic Background: Not reported
ES Cell Line:
Mutant ES Cell Line:
Model Source:
Z_HGFA_2_KD_HM_MO
Model Type:
Genetic
Model Genotype: Wild type
Mutation: Embryos were co-injected with hgfa-E6I6 (5mg/ml) and hgfb-E4I4 (5mg/ml) MOs.
Allele Type: Loss-of-function
Strain of Origin: Wild-type fish strain *AB
Genetic Background: Not reported
ES Cell Line:
Mutant ES Cell Line:
Model Source:
Model Genotype: Wild type
Mutation: Embryos were co-injected with hgfa-E6I6 (5mg/ml) and hgfb-E4I4 (5mg/ml) MOs.
Allele Type: Loss-of-function
Strain of Origin: Wild-type fish strain *AB
Genetic Background: Not reported
ES Cell Line:
Mutant ES Cell Line:
Model Source:
Z_HGFA_1_KD_HM_MO
Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Neuronal migration1
Abnormal
Description: In hgf morphants, only a few facial motor neurons did not complete their migration, while the majority reached r6, compared to controls.
Immunohistochemistry
48 hpf
Not Reported:
Circadian sleep/wake cycle, Communications, Developmental profile, Emotion, Immune response, Learning & memory, Maternal behavior, Molecular profile, Motor phenotype, Neurophysiology, Physiological parameters, Repetitive behavior, Seizure, Sensory, Social behavior
Z_HGFA_2_KD_HM_MO
Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Neuronal differentiation and specification in the brain1
Decreased
Description: hgf double morphants showed a reduction in the number of HuC-positive newly differentiated cerebellar neurons, both in more dorsal positions and mid-ventral positions, compared to controls.
Immunohistochemistry
48 hpf
Cell proliferation: neural precursors1
Decreased
Description: hgf morphants showed a reduction in the rate of midbrain cell proliferation (mitotic index) compared to controls.
Immunohistochemistry
24 hpf
Neuronal differentiation and specification in the brain1
Decreased
Description: hgf double morphants showed a reduction in the number of HuC-positive newly differentiated cerebellar neurons compared to controls.
Immunohistochemistry
72 hpf
Brain development1
Abnormal
Description: Dorsal cerebellar folds are not completely fused in hgf morphants.
Immunohistochemistry
48 hpf
Neuronal migration1
Decreased
Description: hgf morphants showed a slight delay in the migration of phox2a-positive neurons from the dorsal anterior hindbrain to ventral r1 compared to controls.
Immunohistochemistry
24 hpf
Cell proliferation: neural precursors: granule cell precursors1
Decreased
Description: hgf morphants showed a significant (62%) reduction in pH3-positive cells compared to controls.
Immunohistochemistry
24 hpf
Neuronal migration1
Decreased
Description: hgf morphants showed a significant reduction in facial motor neuron migration, with approximately 60% of neurons failing to reach r6, compared to controls.
Immunohistochemistry
48 hpf
Cell proliferation: neural precursors: granule cell precursors1
Decreased
Description: hgf morphants showed a significant (54%) reduction in the rate of cerebellar proliferation (mitotic index) compared to controls.
Immunohistochemistry
24 hpf
Apoptosis1
Increased
Description: hgf morphants showed only a slight increase in cell death throughout the CNS compared to controls.
Acridine orange staining
24 hpf
Mortality/lethality1
Decreased
Description: Morphant embryos were viable at 72 hpf, but died shortly thereafter, probably due to disruption of other developmental processes.
General observations
72 hpf
Gene expression1
Decreased
Description: hgf morphants showed a severe reduction in rora2 expression in the cerebellum compared to controls.
Quantitative pcr (qrt-pcr)
72 hpf
Gene expression1
Decreased
Description: hgf morphants showed a decrease in ptf1a expression comapred to controls.
Quantitative pcr (qrt-pcr)
72 hpf
Gene expression1
Decreased
Description: hgf morphants showed a severe reduction in coe2 expression in the cerebellum compared to controls.
Quantitative pcr (qrt-pcr)
72 hpf
Gene expression1
Decreased
Description: hgf morphants showed a marked reduction in pax6a expression compared to controls.
Quantitative pcr (qrt-pcr)
72 hpf
Gene expression1
Decreased
Description: met morphants showed a marked reduction in reln expression compared to controls.
Quantitative pcr (qrt-pcr)
72 hpf
Gene expression1
Decreased
Description: hgf morphants showed a decrease in ptf1a expression in the anterior region of the dorsal midline comapred to controls.
Quantitative pcr (qrt-pcr)
48 hpf
Not Reported:
Circadian sleep/wake cycle, Communications, Emotion, Immune response, Learning & memory, Maternal behavior, Motor phenotype, Neurophysiology, Physiological parameters, Repetitive behavior, Seizure, Sensory, Social behavior
