PgmNr Z6222: Zebrafish Rfx4 is required for neural tube morphogenesis.

Authors:
Y. Grinblat; I. Sedykh; A. Keller


Institutes
Univ Wisconsin, Madison, WI.


Abstract:

Rfx family of wing-helix transcription factors are key regulators of the core ciliogenesis program in vertebrates. Recently, Rfx genes have been shown to function independently of ciliogenesis, e.g. during brain ventricle morphogenesis. To better understand the mechanism of Rfx gene function during neural tube development, we have generated frame-shift alleles in the zebrafish rfx4 locus using CRISPR/Cas9. Rfx4 mutant embryos develop with a curvature characteristic of disrupted ciliogenesis, as do Rfx4 morphants.   However, transcriptome analysis of Rfx4 mutant vs sibling embryos suggests that the primary role of Rfx4 is to promote expression of neural tube roof plate markers, e.g. zic2a, and floor plate markers, e.g. fox2a.  Further, transcriptome analysis suggests that zebrafish Rfx4 is essential for Hh signaling but does not play a major role in ciliary gene transcription during embryogenesis.  These findings are consistent with a recent mouse study that identified a cilia-independent role for Rfx4 as a transcriptional regulator of foxa2 in the floor plate and zic2 in the roof plate.  Notably, curvature reminiscent of the rfx4 phenotype has been reported in foxa2/monorail mutant zebrafish. Collectively, these data shed light on an important, yet incompletely understood conserved node in the gene regulatory network that controls patterning and morphogenesis of the neural tube.



ZFIN Genetics Index
1. rfx4
2. zic2a
3. foxa2
4. wnt3