Fgf4 is required for left–right patterning of visceral organs in zebrafish

Abstract

Fgf signaling plays essential roles in many developmental events. To investigate the roles of Fgf4 signaling in zebrafish development, we generated Fgf4 knockdown embryos by injection with Fgf4 antisense morpholino oligonucleotides. Randomized LR patterning of visceral organs including the liver, pancreas, and heart was observed in the knockdown embryos. Prominent expression of Fgf4 was observed in the posterior notochord and Kupffer's vesicle region in the early stages of segmentation. Lefty1, lefty2, southpaw, and pitx2 are known to play crucial roles in LR patterning of visceral organs. Fgf4 was essential for the expression of lefty1, which is necessary for the asymmetric expression of southpaw and pitx2 in the lateral plate mesoderm, in the posterior notochord, and the expression of lefty2 and lefty1 in the left cardiac field. Fgf8 is also known to be crucial for the formation of Kupffer's vesicle, which is needed for the LR patterning of visceral organs. In contrast, Fgf4 was required for the formation of cilia in Kupffer's vesicle, indicating that the role of Fgf4 in the LR patterning is quite distinct from that of Fgf8. The present findings indicate that Fgf4 plays a unique role in the LR patterning of visceral organs in zebrafish.

Transcriptome Changes Associated with Protective Immunity in T and B Cell-Deficient <i>Rag1<sup>-/-</sup> </i> Mutant Zebrafish

“…FGF-2 is expressed in stromal cells, macrophages and leukemic cell lines and is involved in physiological and pathological hematopoiesis [48]. FGF4 is vital for the development of visceral organs and is transcriptionally regulated by lymphoid enhancer factor-1 [49] belonging to subfamily of HMG proteins [50]. In our study FGF4 was down regulated in the immunized fish.…”

“…Elevated levels of α-MCH in human plasma have antimicrobial functions [54]. Under inflammatory conditions, MCH receptor (MCHR1) expression was up-regulated on human colonic epithelial cells [49]. In our study fish hematopoietic tissue may have been inflamed due to the injection of E. ictaluri, resulting in up-regulated MCHR1 expression in kidney epithelial cells.…”

Notch signalling regulates left-right asymmetry through ciliary length control

“…To our knowledge, Notch signalling is the first pathway that can both increase or decrease ciliary length, upon upregulation or downregulation, respectively. By contrast, FGF signalling has only been involved in shortening cilia length, (Hong and Dawid, 2009;Yamauchi et al, 2009). Our experiments identify foxj1a, the master motile ciliogenic transcription factor (Yu et al, 2008) as being downstream of DeltaD because it successfully rescued cilia length in aei -/-mutants in a cell-autonomous manner.…”

Far from solved: A perspective on what we know about early mechanisms of left–right asymmetry

“…When the endogenous organizer is ablated and embryonic patterning is rescued by induction of an organizer as early as the 32-cell stage, embryos are normal except that their LR axis is destabilized, showing that an organizer deprived of the orienting events occurring during the first few cleavages cannot orient asymmetry properly, despite the lack of any disruption at the later ciliated node. Furthermore, there are several examples from zebrafish studies indicating that molecular genetic alterations in the cells contributing to the ciliated KV are not sufficient to induce laterality defects (Yamauchi et al, 2009) or produce diminished LR phenotypes compared with genetic knockdown of targets in all cells (Bisgrove et al, 2005).…”