Some of the genes regulated in the thymus of heterozygous mutant animals were also found to be regulated in homozygous mutant embryos such as Ddx6, Higd1b and polypeptides of Ywha 14-3-3 14-3-3 14-3-38] and unpublished data).
The repression of Ras-MAPK signaling by Cno does not account, however, for all the phenotypes detected in cno2 mutant embryos, such as cases of Eve+ progenitor losses (i.e. if Cno were merely inhibiting Ras, in cno2 mutant embryos there would be more positive Ras signaling and, thus, only more Eve+ progenitors should be found).
This loss of actin remodeling proteins has been previously observed in other membrane trafficking mutant embryos such as rab11 (Riggs et al., 2003).
It should also be noted that other cellular processes might also be disrupted by RA and contribute to the phenotypic heterogeneity in Twsg1 mutant embryos, such as premature differentiation induced by increased levels of RA (Laue et al., 2011).
However, the multitude of phenotypes observed in the DME cells of foscrb Y10A mutant embryos, such as persistence of CrbY10A, DPatj and Baz proteins and decrease of Ed expression at the LE, as well as disruption of the supracellular actomyosin cable and disorganised filopodia, suggest that Crb performs also specific functions in the DME.
Indeed, gene ontology analysis shows enrichment for phenotypes that are reminiscent of BRA mutant embryos, such as 'abnormal somite size' (P=9.26×10−24), 'abnormal tail development' (P=1.90×10−22), 'abnormal gastrulation' (P=1.56×10−17) and 'abnormal vascular development' (P=3.29×10−16) (supplementary material Table S4).
If the latter interpretation is correct there should be a similar reduction in proliferation in all tissues in kto mutant embryos, but such a general reduction in proliferation was not detected in a previous study [7].
Hence, the allelic combination of Gli1-CreERT2; resultoM2 could result in Hh signal activation in Hh-responded tissues in such mutant embryos.
Interestingly, some aspects of the mutant phenotype of foscrb Y10A crb GX24 embryos, such as un-coordinated apical constriction, resemble those described for human colon cancer epithelial DLD-1 cells upon RNAi-mediated knock-down of Lulu, the mammalian ortholog of Yurt.
Such ball mutant embryos were viable and hatched (98% of expected; n = 3037 embryos), and we detected no defects in their nervous systems based on staining with the 22C10 monoclonal antibody recognizing the Futsch protein (Fujita et al., 1982), which marks neurons of the central and peripheral nervous system (data not shown).
We tested this idea directly by isolating sensory neurons from NT-3−/− mutant embryos at E13.5 and asked whether such neurons possess a mechanosensitive RA-current.
