Hedgehog signalling is required for cloacal development in the zebrafish embryo

Parkin, Caroline A.; Allen, Claire; Ingham, Philip W.

doi:10.1387/ijdb.082669cp

Cited by 31 publications

(24 citation statements)

References 66 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the zebrafish esophagus and swimbladder, molecular interactions between epithelial Hh and mesenchymal Fgf10 regulate proliferation and differentiation (Korzh et al, 2011). In addition, Hh signaling from the endoderm is required for posterior gut development in zebrafish embryos (Parkin et al, 2009). Thus, smo probably regulates lumen fusion through epithelial-mesenchymal interactions and/or morphogen signaling such as the Bmp or Fgf pathways.…”

Section: Discussionmentioning

confidence: 99%

“…The hedgehog (Hh) pathway is known to be involved in gastrointestinal tract morphogenesis in mammals and cloaca formation in zebrafish Parkin et al, 2009;Ramalho-Santos et al, 2000;Wallace and Pack, 2003). Therefore, we examined lumen formation in embryos mutant for smoothened (smo), the hedgehog co-receptor.…”

Section: Smoothened Mutants Exhibit Impaired Lumen Fusionmentioning

confidence: 99%

See 1 more Smart Citation

Single continuous lumen formation in the zebrafish gut is mediated by smoothened-dependent tissue remodeling

et al. 2014

View full text Add to dashboard Cite

The formation of a single lumen during tubulogenesis is crucial for the development and function of many organs. Although 3D cell culture models have identified molecular mechanisms controlling lumen formation in vitro, their function during vertebrate organogenesis is poorly understood. Using light sheet microscopy and genetic approaches we have investigated single lumen formation in the zebrafish gut. Here we show that during gut development multiple lumens open and enlarge to generate a distinct intermediate, which consists of two adjacent unfused lumens separated by basolateral contacts. We observed that these lumens arise independently from each other along the length of the gut and do not share a continuous apical surface. Resolution of this intermediate into a single, continuous lumen requires the remodeling of contacts between adjacent lumens and subsequent lumen fusion. We show that lumen resolution, but not lumen opening, is impaired in smoothened (smo) mutants, indicating that fluid-driven lumen enlargement and resolution are two distinct processes. Furthermore, we show that smo mutants exhibit perturbations in the Rab11 trafficking pathway and demonstrate that Rab11-mediated trafficking is necessary for single lumen formation. Thus, lumen resolution is a distinct genetically controlled process crucial for single, continuous lumen formation in the zebrafish gut.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Smoothened Mutants Exhibit Impaired Lumen Fusionmentioning

confidence: 99%

Single continuous lumen formation in the zebrafish gut is mediated by smoothened-dependent tissue remodeling

et al. 2014

View full text Add to dashboard Cite

show abstract

“…Recent examination of the zebrafish anogenital system, which undergoes septation, also found a requirement for Hedgehog signaling during cloacal development, with, the most severe anorectal defects occurring in smu (smoothened) mutants or in embryos treated with cyclopamine (Parkin et al, 2009). By contrast, embryos null for shha displayed similar defects to those observed in Shh -/-mice, with some ptc1 expression persistent in the posterior hindgut.…”

Section: Multiphasic Role Of Shh In Anogenital Developmentmentioning

confidence: 96%

Multiphasic and tissue-specific roles of sonic hedgehog in cloacal septation and external genitalia development

et al. 2009

View full text Add to dashboard Cite

Malformations of the external genitalia are among the most common congenital anomalies in humans. The urogenital and anorectal sinuses develop from the embryonic cloaca, and the penis and clitoris develop from the genital tubercle. Within the genital tubercle, the endodermally derived urethral epithelium functions as an organizer and expresses sonic hedgehog (Shh). Shh knockout mice lack external genitalia and have a persistent cloaca. This identified an early requirement for Shh, but precluded analysis of its later role in the genital tubercle. We conducted temporally controlled deletions of Shh and report that Shh is required continuously through the onset of sexual differentiation. Shh function is divisible into two temporal phases; an anogenital phase, during which Shh regulates outgrowth and patterning of the genital tubercle and septation of the cloaca, and a later external genital phase, during which Shh regulates urethral tube closure. Disruption of Shh function during the anogenital phase causes coordinated anorectal and genitourinary malformations, whereas inactivation during the external genital phase causes hypospadias. Shh directs cloacal septation by promoting cell proliferation in adjacent urorectal septum mesenchyme. Additionally, conditional inactivation of smoothened in the genital ectoderm and cloacal/urethral endoderm shows that the ectoderm is a direct target of Shh and is required for urethral tube closure, highlighting a novel role for genital ectoderm in urethragenesis. Identification of the stages during which disruption of Shh results in either isolated or coordinated malformations of anorectal and external genital organs provides a new tool for investigating the etiology of anogenital malformations in humans.

show abstract

“…All experiments conducted were approved by the University of Oregon Institutional Animal Care and Use Committee (IACUC). Zebrafish lines were as described: ihha hu2131 (Parkin et al, 2009), ptch1 tj222 (Koudijs et al, 2005), Tg(sp7:EGFP)b1212 and trps1 J1271aGt (Talbot et al, 2010). ihha mutants were identified by PCR genotyping with the primers ihhaf6 (5Ј-CTGTGCCACCGTACCACTC-3Ј) and ihhar5 (5Ј-GCTACATTTGGACTAAACTGCAT-3Ј), and wild-type allele cut with NspI.…”

Section: Zebrafish Linesmentioning

confidence: 99%

“…The opercle (Op) of zebrafish larvae homozygous for the putative null ihha hu2131 allele (Parkin et al, 2009) is malformed in shape and reduced in size compared with wild type (Fig. 1A,B).…”

Section: Opercle Morphogenesis Is Altered In Ihha Mutantsmentioning

confidence: 99%

Hedgehog-dependent proliferation drives modular growth during morphogenesis of a dermal bone

2012

View full text Add to dashboard Cite

SUMMARYIn the developing skeleton, dermal bone morphogenesis includes the balanced proliferation, recruitment and differentiation of osteoblast precursors, yet how bones acquire unique morphologies is unknown. We show that Hedgehog (Hh) signaling mediates bone shaping during early morphogenesis of the opercle (Op), a well characterized dermal bone of the zebrafish craniofacial skeleton. ihha is specifically expressed in a local population of active osteoblasts along the principal growing edge of the bone. Mutational studies show that Hh signaling by this osteoblast population is both necessary and sufficient for full recruitment of pre-osteoblasts into the signaling population. Loss of ihha function results in locally reduced proliferation of pre-osteoblasts and consequent reductions in recruitment into the osteoblast pool, reduced bone edge length and reduced outgrowth. Conversely, hyperactive Hh signaling in ptch1 mutants causes opposite defects in proliferation and growth. Time-lapse microscopy of early Op morphogenesis using transgenically labeled osteoblasts demonstrates that ihha-dependent bone development is not only region specific, but also begins exactly at the onset of a second phase of morphogenesis, when the early bone begins to reshape into a more complex form. These features strongly support a hypothesis that dermal bone development is modular, with different gene sets functioning at specific times and locations to pattern growth. The Hh-dependent module is not limited to this second phase of bone growth: during later larval development, the Op is fused along the dysmorphic edge to adjacent dermal bones. Hence, patterning within a module may include adjacent regions of functionally related bones and might require that signaling pathways function over an extended period of development.

show abstract

Hedgehog signalling is required for cloacal development in the zebrafish embryo

Cited by 31 publications

References 66 publications

Single continuous lumen formation in the zebrafish gut is mediated by smoothened-dependent tissue remodeling

Single continuous lumen formation in the zebrafish gut is mediated by smoothened-dependent tissue remodeling

Multiphasic and tissue-specific roles of sonic hedgehog in cloacal septation and external genitalia development

Hedgehog-dependent proliferation drives modular growth during morphogenesis of a dermal bone

Contact Info

Product

Resources

About