Our findings, that CFC kinase-impaired mutant alleles behave similar to kinase-active mutant alleles in vivo, are reminiscent of the action of both gain-of-function Noonan and loss-of-function LEOPARD Shp2 disease alleles to promote ectopic wing vein growth in Drosophila (13, 14), and cell movement phenotypes in zebrafish (15).
With this "double" TRH-Gal4 line we quantified the "movement" phenotype and observed an increase in the numbers of flies showing the phenotype from 22 to 50% (data not shown).
Unc5 was originally identified as a mutation in the nematode C. elegans resulting in an uncoordinated movement phenotype [9].
It was initially termed UNC-51, since its loss resulted in an uncoordinated movement phenotype [ 23] and has been originally regarded as an essential factor for neuronal development.
In addition to an increased frequency of spontaneous contractions at 30 hpf (Fig. 3A), which could indicate that neurons are hyperexcitable, several other abnormal movement phenotypes were detected in kcnj10a morphants at 120 hpf.
In addition, we find that the cell movement phenotypes of both the kinase-activating and kinase-impaired CFC alleles can be prevented by treatment with specific MEK inhibitors.
The movement phenotypes of larvae and surviving lam adults recall effects of mutations in the human LMNA gene.
As positive controls for the RNAi we chose genes that produce distinct phenotypes; gpb-1, for which mutants are embryonic lethal, and unc-22, which results in a post-embryonic uncoordinated movements phenotype (Unc) [ 58, 59].
This resulted in a striking phenotype, in which flagellar movement of the forming microgametes commenced while the gametocyte was still inside the host cell.
Consistent with a general role of TXDC-9 in microtubule dynamics, animals homozygous for the txdc-9 mutation were defective in movement, a phenotype also seen when microtubules are disrupted by benomyl and other microtubule drugs (Chalfie and Thomson 1982).
