2020
DOI: 10.1101/2020.12.30.424496
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The Broad Role of Nkx3.2 in the Development of the Zebrafish Axial Skeleton

Abstract: The transcription factor Nkx3.2 (Bapx1) is an important chondrocyte maturation inhibitor. Previous Nkx3.2 knock-down and overexpression studies in non-mammalian gnathostomes have focused on its role in primary jaw joint development, while little is known about the function of this gene in broader skeletal development. We generated CRISPR/Cas9 knockout of nkx3.2 in zebrafish and applied a range of techniques to characterize skeletal phenotypes at developmental stages from larva to adult, revealing fusions in bo… Show more

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Cited by 4 publications
(11 citation statements)
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“…This role of Gdf5 as a promoter of chondrocyte maturation is opposite to the function of NK 3 homeobox 2 (Nkx3.2) transcription factor, which is a well-known chondrocyte maturation inhibitor (Provot et al, 2006). Interestingly, previously reported nkx3.2 mutant zebrafish display increased length of the proximal radials of the dorsal and anal fins (Waldmann et al, 2020), which is the opposite phenotypic outcome to what we saw in gdf5 mutant zebrafish fins.…”
Section: Discussioncontrasting
confidence: 87%
“…This role of Gdf5 as a promoter of chondrocyte maturation is opposite to the function of NK 3 homeobox 2 (Nkx3.2) transcription factor, which is a well-known chondrocyte maturation inhibitor (Provot et al, 2006). Interestingly, previously reported nkx3.2 mutant zebrafish display increased length of the proximal radials of the dorsal and anal fins (Waldmann et al, 2020), which is the opposite phenotypic outcome to what we saw in gdf5 mutant zebrafish fins.…”
Section: Discussioncontrasting
confidence: 87%
“…If we assume elephant shark nkx3.2 gene expression mirrors that of elasmobranchs and that JRS1 drives nkx3.2 gene expression in all pharyngeal arches, our results would support the conclusion that much of the gene regulatory landscape of osteichthyan mandibular joints is found more broadly in the pharyngeal arches of chondrichthyans (Hirschberger et al, 2021). JRS1 knockout did not phenocopy the striking jaw joint fusion seen in zebrafish nkx3.2 gene knockout mutants (Miyashita et al, 2020;Waldmann et al, 2021), suggesting this enhancer is not essential for nkx3.2 expression at the time points analysed. However, as a subtle jaw joint phenotype was still evident in homozygous mutants, most notably the reduction of the RAP and partial fusion observed at 5-9 dpf, the loss of JRS1 must have some local effect on nkx3.2 expression, consistent with the specific jaw joint activity seen in transgenic reporter fish.…”
Section: Discussionsupporting
confidence: 57%
“…In order to characterize the nkx3.2 (JRS1):mCherry expressing cells in nkx3.2 gene mutants we incrossed previously reported nkx3.2 +/uu2803 mutant alleles (Waldmann et al, 2021) with nkx3.2 (JRS1):mCherry/ sox10 :egfp background and used these heterozygotes to generate homozygous nkx3.2 uu2803/uu2803 mutants (abbreviated to nkx3.2 -/- ). Notably, nkx3.2 (JRS1):mCherry expressing cells were detected lining the outside of the cartilage in the fused jaw joint region of nkx3.2 -/- mutants at 3-5 dpf (Figure 3E-F, E’-F’).…”
Section: Resultsmentioning
confidence: 99%
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