ZFIN ID: ZDB-PUB-171216-6
Zebrafish Rfx4 controls dorsal and ventral midline formation in the neural tube
Sedykh, I., Keller, A.N., Yoon, B., Roberson, L., Moskvin, O.V., Grinblat, Y.
Date: 2017
Source: Developmental dynamics : an official publication of the American Association of Anatomists 247(4): 650-659 (Journal)
Registered Authors: Grinblat, Yevgenya, Roberson, Laura
Keywords: Hh signaling, Rfx4, Zic, foxa2, neural tube, zebrafish
Microarrays: GEO:GSE101390
MeSH Terms: none
PubMed: 29243319 Full text @ Dev. Dyn.
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ABSTRACT
Rfx winged-helix transcription factors, best known as key regulators of core ciliogenesis, also play ciliogenesis-independent roles during neural development. Mammalian Rfx4 controls neural tube morphogenesis via both mechanisms.
We set out to identify conserved aspects of rfx4 gene function during vertebrate development and to establish a new genetic model in which to analyze these mechanisms further. To this end, we have generated frame-shift alleles in the zebrafish rfx4 locus using CRISPR/Cas9 mutagenesis. Using RNAseq-based transcriptome analysis, in situ hybridization and immunostaining we identified a requirement for zebrafish rfx4 in the forming midlines of the caudal neural tube. These functions are mediated, least in part, through transcriptional regulation of several zic genes in the dorsal hindbrain and of foxa2 in the ventral hindbrain and spinal cord (floor plate).
The midline patterning functions of rfx4 are conserved, since rfx4 regulates transcription of foxa2 and zic2 in zebrafish and in mouse. In contrast, zebrafish rfx4 function is dispensable for forebrain morphogenesis, while mouse rfx4 is required for normal formation of forebrain ventricles in a ciliogenesis-dependent manner. Collectively, this report identifies conserved aspects of rfx4 function and establishes a robust new genetic model for in-depth dissection of these mechanisms. This article is protected by copyright. All rights reserved.
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