<i>vhnf1</i>integrates global RA patterning and local FGF signals to direct posterior hindbrain development in zebrafish

Hernandez, Rafael E.; Rikhof, Holly A.; Bachmann, Ruxandra; Moens, Cecilia B.

doi:10.1242/dev.01297

Cited by 105 publications

(143 citation statements)

References 49 publications

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“…vhnf1 positively controls val expression in the hindbrain (Wiellette and Sive, 2003;Hernandez et al, 2004). As expected, AP patterning phenotypes are observed in the inner ear of vhnf1 mutants, which display an expansion or a duplication of the expression of anterior otic genes such as hmx3, fgf8 and pax5.…”

Section: Hindbrain Segmentation and Otic Patterningsupporting

confidence: 72%

Patterning and cell fate in ear development

Alsina¹,

Giráldez²,

Pujades³

2009

Int. J. Dev. Biol.

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The inner ear is a complex structure responsible for the senses of audition and balance in vertebrates. The ear is organised into different sense organs that are specialised to detect specific stimuli such as sound and linear or angular accelerations. The elementary sensory unit of the ear consists of hair cells, supporting cells, neurons and Schwann cells. Hair cells are the mechano-electrical transducing elements, and otic neurons convey information coded in electrical impulses to the brain. With the exception of the Schwann cells, all cellular elements of the inner ear derive from the otic placode. This is an ectodermal thickening that is specified in the head ectoderm adjacent to the caudal hindbrain. The complex organisation of the ear requires precise coupling of regional specification and cell fate decisions during development, i.e. specificity in defining particular spatial domains containing particular cell types. Those decisions are taken early in development and are the subject of this article. We review here recent work on: i) early patterning of the otic placode, ii) the role of neural tube signals in the patterning of the otic vesicle, and iii) the genes underlying cell fate determination of neurons and sensory hair cells. KEY WORDS: placode, otic vesicle, proneural, hindbrain, patterning State of the artThe inner ear is one major sensory organ of the head and it is responsible for the perception of sound and balance in vertebrates. In the adult, it is arranged in a highly complex threedimensional structure, named the membranous labyrinth, composed of a closed epithelial layer that is diversified into specific regions that contain the sensory elements (Fig. 1A). The sensory epithelium consists of hair cells, and supporting cells disposed in a cellular mosaic (Fig. 1B) (Adam et al., 1998;Fritzsch et al., 2000). Mechanosensory information is transduced by the hair cells that release transmitters which activate afferent bipolar sensory neurons which, in turn, transmit the information to second order neurons in the brainstem. The membranous labyrinth is subdivided into vestibular and auditory regions. The vestibule forms the dorsal part of the labyrinth and is responsible for the senses of motion and position. It comprises the three cristae, the sensory organs located at the basis of three orthogonally arranged semi-circular canals, and the utricle and saccule, which contain two additional sensory organs, the maculae. The ventral auditory part is more diverse. In mammals it is composed of the cochlea, a coiled structure whose sensory epithelium is called the organ of Corti. In birds, the auditory region is composed of the basilar papilla, while in fish the saccule and lagena are both involved in hearing (Fig. 1A) , 2003). In jawed vertebrates, the adult inner ear is highly regionalised along its three axes. In addition to the dorso-ventral (DV) subdivision into vestibular and auditory regions, an asymmetry along the medio-lateral (ML) axis is also obvious with, for instance, the endolymphat...

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Section: Hindbrain Segmentation and Otic Patterningsupporting

confidence: 72%

Patterning and cell fate in ear development

Alsina¹,

Giráldez²,

Pujades³

2009

Int. J. Dev. Biol.

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“…The divergent expression patterns of the duplicated pairs in zebrafish indicate areas where functions may have been divided between the paralogs or where new functions may have been gained. The expression patterns also suggest that the RARs may have specific roles in mediating RA signaling in particular contexts, such as a putative role of rarab in controlling val expression in r5/r6 of the hindbrain or a potential function of rargb in the neural crest (Hernandez et al, 2004). Therefore, comparing the complete set of zebrafish rar genes reveals common trends in paralog pairs in addition to defining conserved and distinct expression patterns that suggest specific roles in mediating RA signaling.…”

Section: Rar Expression From the Tailbud Stage Through 24 Hours Post-mentioning

confidence: 92%

“…3D). RA signaling is required for r5/r6 specification through regulation of val expression (Hernandez et al, 2004). Given the upregulation of rarab in the r5/r6 region and the known role of RA signaling in specifying r5/r6, this expression pattern suggests that rarab may play a specific role in mediating the RA signaling in r5/r6.…”

Section: Rar Expression From the Tailbud Stage Through 24 Hours Post-mentioning

confidence: 93%

Comparison of the expression patterns of newly identified zebrafish retinoic acid and retinoid X receptors

Waxman

Yelon

2006

Developmental Dynamics

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“…RA directly regulates gene expression through its nuclear hormone receptor (RAR) and co-receptor (RXR), which bind RA response elements (RAREs) in the enhancers of target genes (Bastien and Rochette-Egly, 2004). In the hindbrain, RA regulates the expression of 3Ј-Hox genes through direct (in the case of Hox-1 and Hox-4 genes) or indirect (in the case of Hox-3 genes) mechanisms (Gould et al, 1998;Hernandez et al, 2004;Marshall et al, 1994;Nolte et al, 2003;Studer et al, 1994;Zhang et al, 2000). Other anterior RAresponsive genes (Hox-1 family genes) are expressed earlier and at lower RA concentrations than the more-posterior RA-responsive genes (Hox-4 family genes) (Dupe and Lumsden, 2001;Maves and Kimmel, 2005;Simeone et al, 1990).…”

Section: Introductionmentioning

confidence: 99%

Cyp26 enzymes generate the retinoic acid response pattern necessary for hindbrain development

et al. 2007

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Retinoic acid (RA) is essential for normal vertebrate development,including the patterning of the central nervous system. During early embryogenesis, RA is produced in the trunk mesoderm through the metabolism of vitamin A derived from the maternal diet and behaves as a morphogen in the developing hindbrain where it specifies nested domains of Hox gene expression. The loss of endogenous sources of RA can be rescued by treatment with a uniform concentration of exogenous RA, indicating that domains of RA responsiveness can be shaped by mechanisms other than the simple diffusion of RA from a localized posterior source. Here, we show that the cytochrome p450 enzymes of the Cyp26 class, which metabolize RA into polar derivatives,function redundantly to shape RA-dependent gene-expression domains during hindbrain development. In zebrafish embryos depleted of the orthologs of the three mammalian CYP26 genes CYP26A1, CYP26B1 and CYP26C1, the entire hindbrain expresses RA-responsive genes that are normally restricted to nested domains in the posterior hindbrain. Furthermore,we show that Cyp26 enzymes are essential for exogenous RA to rescue hindbrain patterning in RA-depleted embryos. We present a `gradient-free' model for hindbrain patterning in which differential RA responsiveness along the hindbrain anterior-posterior axis is shaped primarily by the dynamic expression of RA-degrading enzymes.

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vhnf1integrates global RA patterning and local FGF signals to direct posterior hindbrain development in zebrafish

Cited by 105 publications

References 49 publications

Patterning and cell fate in ear development

Patterning and cell fate in ear development

Comparison of the expression patterns of newly identified zebrafish retinoic acid and retinoid X receptors

Cyp26 enzymes generate the retinoic acid response pattern necessary for hindbrain development

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