Anteroposterior patterning of the zebrafish ear through Fgf- and Hh-dependent regulation of<i>hmx3a</i>expression

Hartwell, Ryan D.; England, Samantha J.; Monk, Nicholas; Hateren, Nicholas J. van; Baxendale, Sarah; Marzo, Mar; Lewis, Katharine E.; Whitfield, Tanya T.

doi:10.1101/451963

Cited by 3 publications

(11 citation statements)

References 53 publications

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“…Consistent with previous reports, both of these genes are also expressed in the lateral line and developing ear (Fig. 1;Adamska et al, 2000;Feng and Xu, 2010;Hartwell et al, 2019) as well as distinct regions of the brain (data not shown).…”

Section: Introductionsupporting

confidence: 93%

“…Previous research has shown that Hmx2 and Hmx3 have crucial functions in ear development in mouse and our recent work shows that this is also the case for Hmx3a in zebrafish (Hartwell et al, 2019;Wang et al, 2001;Wang et al, 2004;Wang and Lufkin, 2005;Wang et al, 1998; see also Feng and Xu, 2010). These genes are also required for correct specification of the mouse hypothalmus (Wang et al, 2004) and morpholino knock-down experiments have suggested that they are required for correct progression of the lateral line in zebrafish (Feng and Xu, 2010).…”

Section: Introductionsupporting

confidence: 66%

“…As our morpholino-injected embryos had fused otoliths, and our previous analyses had shown that this was also the case in hmx3a SU3 mutants (Hartwell et al, 2019), we expected that hmx2 mutants would have this same phenotype. However, we did not detect any otolith fusion phenotypes in embryos homozygous for four different hmx2 alleles (hmx2 SU35 , hmx2 SU36 , hmx2 SU37 , hmx2 SU38 ; Fig.…”

Section: Introductionsupporting

confidence: 53%

“…The generation of the hmx3a SU3 allele was previously described (Hartwell et al, 2019). With the exception of hmx3a sa23054 (which was generated as part of the Zebrafish Mutation Project and obtained from ZIRC), we generated all of the other hmx2, hmx3a and hmx2/3a mutants described in this paper using CRISPR mutagenesis.…”

Section: Crispr Mutagenesis and Screeningmentioning

confidence: 99%

“…4, Fig. 5E, K, Table 3, also see (Hartwell et al, 2019) for a detailed description of the hmx3a SU3 ear phenotype). When we examined the spinal cords of embryos homozygous for these mutant alleles, we observed a statistically significant reduction in the number of glutamatergic cells, but in each case the change was smaller than we had previously observed for morpholino- Table 2).…”

Section: Introductionmentioning

confidence: 98%

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Hmx3a has essential functions in zebrafish spinal cord, ear and lateral line development

England

Cerda

Kowalchuk

et al. 2020

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Homeodomain-containing transcription factors have crucial functions in most aspects of cellular function and embryonic development in both animals and plants. Hmx proteins are a sub-family of NK homeodomain proteins and previous research has shown that they have crucial functions in the development of sensory structures such as the eye and the ear. However, the functions of Hmx proteins in spinal cord development have not been analyzed.Here we show that zebrafish hmx2 and hmx3a are co-expressed in spinal dI2 and V1 neurons, whereas hmx3b, hmx1 and hmx4 are not expressed in the spinal cord. Using mutational analyses, we demonstrate that, in addition to its previously demonstrated role in ear development, Hmx3a is required for survival to adulthood, lateral line progression and correct specification of spinal interneuron neurotransmitter fates. However, despite the fact that hmx2 and hmx3a have similar expression patterns during embryonic development, we have not detected any requirement for Hmx2 in these developmental processes, even when almost all of the hmx2 locus is deleted. We have also not detected any redundancy between hmx2 and hmx3a: double mutants have identical phenotypes to hmx3a single mutants. Even more surprisingly, we have found that Hmx3a does not require its homeodomain for its roles in viability or embryonic development. This is, to our knowledge, the first time that such a prototypical homeodomain protein has been shown not to require its homeodomain.Hmx2 in viability, or otolith, lateral line or specification of spinal interneuron neurotransmitter fates, even when almost all of the hmx2 locus is deleted (in our most severe mutant allele, hmx2 SU39 , only 84 nucleotides of 5' sequence and 57 nucleotides of 3' coding sequence remain). We have also not detected any redundancy between hmx2 and hmx3a: hmx2;hmx3a double mutants have identical phenotypes to severe hmx3a single mutants. Even more surprisingly, we have found that Hmx3a does not require its homeodomain for its roles in viability or embryonic development. This is, to our knowledge, the first time that such a prototypical homeodomain protein has been shown not to require its homeodomain.

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Section: Introductionsupporting

confidence: 93%

Section: Introductionsupporting

confidence: 66%

Section: Introductionsupporting

confidence: 53%

Section: Crispr Mutagenesis and Screeningmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

See 3 more Smart Citations

Hmx3a has essential functions in zebrafish spinal cord, ear and lateral line development

England

Cerda

Kowalchuk

et al. 2020

Preprint

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Cilia in the developing zebrafish ear

Whitfield

2019

Phil. Trans. R. Soc. B

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The inner ear, which mediates the senses of hearing and balance, derives from a simple ectodermal vesicle in the vertebrate embryo. In the zebrafish, the otic placode and vesicle express a whole suite of genes required for ciliogenesis and ciliary motility. Every cell of the otic epithelium is ciliated at early stages; at least three different ciliary subtypes can be distinguished on the basis of length, motility, genetic requirements and function. In the early otic vesicle, most cilia are short and immotile. Long, immotile kinocilia on the first sensory hair cells tether the otoliths, biomineralized aggregates of calcium carbonate and protein. Small numbers of motile cilia at the poles of the otic vesicle contribute to the accuracy of otolith tethering, but neither the presence of cilia nor ciliary motility is absolutely required for this process. Instead, otolith tethering is dependent on the presence of hair cells and the function of the glycoprotein Otogelin. Otic cilia or ciliary proteins also mediate sensitivity to ototoxins and coordinate responses to extracellular signals. Other studies are beginning to unravel the role of ciliary proteins in cellular compartments other than the kinocilium, where they are important for the integrity and survival of the sensory hair cell. This article is part of the Theo Murphy meeting issue ‘Unity and diversity of cilia in locomotion and transport’.

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Bmper is required for morphogenesis of the anterior and posterior semicircular canal ducts in the developing zebrafish inner ear

Baxendale

et al. 2021

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BMP signalling is known to have a conserved function in development of the semicircular canal system of the vertebrate inner ear, but its regulation, target genes and effects on cell behaviour during otic morphogenesis are not fully understood. We have characterised the effects of mutations in the zebrafish gene bmper, which codes for a regulator of BMP signalling with both pro- and anti-BMP roles in different developmental contexts. The inner ears of bmper mutant embryos develop with truncations of the anterior and posterior semicircular canal ducts. To image the developing ear in live embryos, we have exploited a new transgenic line, Tg(smad6b:EGFP), which exhibits strong GFP expression in the otic epithelium. Morphometric analysis indicates defects in the bmper mutant ear from early stages of semicircular canal formation, correlating with a specific reduction in BMP signalling activity and specific loss of dlx5a expression in dorsal otic epithelium. Subsequent changes to cell shape occur at the truncation site and the dorsolateral septum. The bmper mutations that we describe are adult viable; truncation of the anterior and posterior semicircular canal ducts persists into adulthood. Our results argue against a major role for Bmper in specification of the pre-placodal region, induction of the otic placode, or development of the neural crest, processes in which Bmper function has previously been implicated. Instead, we conclude that a key requirement for Bmper function in the zebrafish is to promote BMP signalling during patterning and morphogenesis of the semicircular canal system.

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Anteroposterior patterning of the zebrafish ear through Fgf- and Hh-dependent regulation ofhmx3aexpression

Cited by 3 publications

References 53 publications

Hmx3a has essential functions in zebrafish spinal cord, ear and lateral line development

Hmx3a has essential functions in zebrafish spinal cord, ear and lateral line development

Cilia in the developing zebrafish ear

Bmper is required for morphogenesis of the anterior and posterior semicircular canal ducts in the developing zebrafish inner ear

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