Analysis of hindbrain patterning defects caused by the kreislerenu mutation reveals multiple roles of Kreisler in hindbrain segmentation

Sadl, Virginia S.; Sing, Angela; Mar, Lynn; Jin, Fuzi; Cordes, Sabine P.

doi:10.1002/dvdy.10279

Cited by 33 publications

(36 citation statements)

References 21 publications

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“…Kreisler (MAFB) encodes a basic domain leucine zipper (bZip) transcription factor of the MAF subfamily and is expressed in mouse podocytes of capillary loop-stage glomeruli (Sadl et al, 2002). It also has an important role in hindbrain segmentation (Sadl et al, 2003). Pod1 and kreisler mutations in mice result in similar phenotypes: glomerular development is arrested at the single capillary loop stage (Quaggin et al, 1999;Sadl et al, 2002), and the podocytes remain as columnar-shaped cells that have lost their lateral cell-cell attachments but remain fully adhered to the GBM without any foot processes.…”

Section: Pod1 and Kreislermentioning

confidence: 99%

Development of the renal glomerulus: good neighbors and good fences

2008

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The glomerulus of the mammalian kidney is an intricate structure that contains an unusual filtration barrier that retains higher molecular weight proteins and blood cells in the circulation. Recent studies have changed our conception of the glomerulus from a relatively static structure to a dynamic one, whose integrity depends on signaling between the three major cell lineages: podocytes, endothelial and mesangial cells. Research into the signaling pathways that control glomerular development and then maintain glomerular integrity and function has recently identified several genes, such as the nephrin and Wilms' tumor 1 genes, that are mutated in human kidney disease.

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Section: Pod1 and Kreislermentioning

confidence: 99%

Development of the renal glomerulus: good neighbors and good fences

2008

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“…Immunofluorescence was performed on 10 mM frozen sections prepared as previously described (Sadl et al, 2003). Imaging was performed on Nikon Eclipse 80i fluorescence microscope with Nikon DS-Ri1 Camera.…”

Section: Micementioning

confidence: 99%

“…The original X-ray-induced Mafb mouse mutation, kreisler (kr), is a near-perfect chromosomal inversion that abolishes rhombomere-specific Mafb expression (Cordes and Barsh, 1994). In kr/kr mutants and in mouse embryos homozygous for the severely hypomorphic or null allele kr enu , the r5-r6 domain does not develop properly, Hox genes expressed in the hindbrain are misregulated, and morphological segmentation in the posterior hindbrain (r4-r7) is lost (Cordes and Barsh, 1994;Frohman et al, 1993;McKay et al, 1994;Sadl et al, 2003). Mafb has been shown to directly activate rhombomere-specific expression of Hoxa3 and Hoxb3 (Manzanares et al, 1999;Manzanares et al, 1997;Yau et al, 2002), but whether it directly regulates other Hox genes is unknown.…”

Section: Introductionmentioning

confidence: 99%

Cdx1 refines positional identity of the vertebrate hindbrain by directly repressingMafbexpression

et al. 2011

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SUMMARYAn interplay of transcription factors interprets signalling pathways to define anteroposterior positions along the vertebrate axis. In the hindbrain, these transcription factors prompt the position-appropriate appearance of seven to eight segmental structures, known as rhombomeres (r1-r8). The evolutionarily conserved Cdx caudal-type homeodomain transcription factors help specify the vertebrate trunk and tail but have not been shown to directly regulate hindbrain patterning genes. Mafb (Kreisler, Krml1, valentino), a basic domain leucine zipper transcription factor, is required for development of r5 and r6 and is the first gene to show restricted expression within these two segments. The homeodomain protein vHnf1 (Hnf1b) directly activates Mafb expression. vHnf1 and Mafb share an anterior expression limit at the r4/r5 boundary but vHnf1 expression extends beyond the posterior limit of Mafb and, therefore, cannot establish the posterior Mafb expression boundary. Upon identifying regulatory sequences responsible for posterior Mafb repression, we have used in situ hybridization, immunofluorescence and chromatin immunoprecipitation (ChIP) analyses to determine that Cdx1 directly inhibits early Mafb expression in the neural tube posterior of the r6/r7 boundary, which is the anteriormost boundary of Cdx1 expression in the hindbrain. Cdx1 dependent repression of Mafb is transient. After the 10-somite stage, another mechanism acts to restrict Mafb expression in its normal r5 and r6 domain, even in the absence of Cdx1. Our findings identify Mafb as one of the earliest direct targets of Cdx1 and show that Cdx1 plays a direct role in early hindbrain patterning. Thus, just as Cdx2 and Cdx4 govern the trunk-to-tail transition, Cdx1 may regulate the hindbrain-to-spinal cord transition.

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“…kreisler is not a null mutant for MafB but rather a regulation mutant, which abolishes MafB expression in r5/r6 and activates it in r3 (Eichmann et al, 1997;Giudicelli et al, 2003). More recently however, the essential function of MafB in regulating the maintenance and expansion of r5 and specification of r6 has been confirmed using a mouse mutant obtained by ENU mutagenesis (Sadl et al, 2003) and in zebrafish, where several mutant alleles of valentino (val), the zebrafish MafB gene, have been obtained Prince et al, 1998). Among other regulatory functions, MafB is necessary for the expression in r5 of krox20, a gene required for the formation and specification of r3 and r5 (Schneider-Maunoury et al, 1993;Schneider-Maunoury et al, 1997;Voiculescu et al, 2001).…”

Section: Caudal Hindbrain Patterningmentioning

confidence: 99%

“…The phenotype of MafB loss-of-function has first been studied in the mouse mutant kreisler, named accordingly to its circling behavior. In the hindbrain, the kreisler mutant displays a loss of r5 and a misspecification of r6 (McKay et al, 1994;Sadl et al, 2003). kreisler is not a null mutant for MafB but rather a regulation mutant, which abolishes MafB expression in r5/r6 and activates it in r3 (Eichmann et al, 1997;Giudicelli et al, 2003).…”

Section: Caudal Hindbrain Patterningmentioning

confidence: 99%

Hindbrain signals in otic regionalization: walk on the wild side

Schneider‐Maunoury¹,

Pujades²

2007

Int. J. Dev. Biol.

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The inner ear, the sensory organ responsible for hearing and balance, contains specialized sensory and non-sensory epithelia arranged in a highly complex three-dimensional structure. To achieve this level of complexity, a tight coordination between morphogenesis and cell fate specification is essential during otic development. Tissues surrounding the otic primordium and more particularly the adjacent segmented hindbrain, have been implicated in conferring signals required for inner ear development. In this review, we present the current view on the role of hindbrain signals in axial specification of the inner ear. The functional analysis of mutants of hindbrain segmentation genes, as well as the investigation of signaling pathways potentially involved, all point to an essential role of FGF, Wnt and Hh signaling in otic regionalization. However, these data provide conflicting evidence regarding the involvement of hindbrain signals in otic regionalization in fish and in amniotes. We discuss the possible origin of these differences. KEY WORDS: hindbrain, patterning, otic regionalization, FGF signaling Basic structure of the adult inner earThe vertebrate inner ear is a sensory organ responsible for the senses of hearing, balance and detection of acceleration. It consists of a closed epithelial structure, the membranous labyrinth, composed of several sensory and non-sensory structures and surrounded by a bony capsule. The mechanosensory function of the inner ear is provided by the hair cells, which, along with supporting and secretory cells, are contained in the sensory epithelia. Hair cells are innervated by sensory neurons of the vestibular and acoustic ganglia that project to the vestibular and auditory nuclei 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 (Figure 1). In jawed vertebrates, the adult inner ear is highly regionalised along its three axes. In addition to the dorso-ventral (DV) subdivision Int. J. Dev. Biol. 51: 495-506 (2007) doi: 10.1387/ijdb.072345ss into vestibular and auditory regions, an asymmetry along the medio-lateral (ML) axis is also obvious with, for instance, the endolymphatic sac and duct located in the medial part, close to the brain. The whole structure also shows pronounced anteroposterior (AP) asymmetry (Figure 1).How are these asymmetries established during ear development? What are the signals involved in establishing thes...

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Analysis of hindbrain patterning defects caused by the kreisler^enu mutation reveals multiple roles of Kreisler in hindbrain segmentation

Abstract: The embryonic hindbrain is subdivided into eight subunits, termed rhombomeres (r1-r8

Cited by 33 publications

References 21 publications

Development of the renal glomerulus: good neighbors and good fences

Development of the renal glomerulus: good neighbors and good fences

Cdx1 refines positional identity of the vertebrate hindbrain by directly repressingMafbexpression

Hindbrain signals in otic regionalization: walk on the wild side

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