The development of the male genitourinary system. I. The origin of the urorectal septum and the formation of the perineum

Hynes, Patrick; Fraher, John

doi:10.1016/j.bjps.2003.08.019

Cited by 64 publications

(56 citation statements)

References 16 publications

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“…Initiation and outgrowth of the GT primordia also critically influence anorectal/urogenital organ development (Hynes and Fraher, 2004), as revealed by the fact that Shh KO mutants display not only GT agenesis, but also a persistent cloaca . Gli2 and some conditional Shh mutant embryos show a severe form of defects for UPE formation in the GT.…”

Section: ;Ctnnb1mentioning

confidence: 99%

Dosage-dependent hedgehog signals integrated with Wnt/β-catenin signaling regulate external genitalia formation as an appendicular program

et al. 2009

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Embryonic appendicular structures, such as the limb buds and the developing external genitalia, are suitable models with which to analyze the reciprocal interactions of growth factors in the regulation of outgrowth. Although several studies have evaluated the individual functions of different growth factors in appendicular growth, the coordinated function and integration of input from multiple signaling cascades is poorly understood. We demonstrate that a novel signaling cascade governs formation of the embryonic external genitalia [genital tubercle (GT)]. We show that the dosage of Shh signal is tightly associated with subsequent levels of Wnt/-catenin activity and the extent of external genitalia outgrowth. In Shh-null mouse embryos, both expression of Wnt ligands and Wnt/-catenin signaling activity are downregulated. -catenin gain-of-function mutation rescues defective GT outgrowth and Fgf8 expression in Shh-null embryos. These data indicate that Wnt/-catenin signaling in the distal urethral epithelium acts downstream of Shh signaling during GT outgrowth. The current data also suggest that Wnt/-catenin regulates Fgf8 expression via Lef/Tcf binding sites in a 3Ј conserved enhancer. Fgf8 induces phosphorylation of Erk1/2 and cell proliferation in the GT mesenchyme in vitro, yet Fgf4/8 compound-mutant phenotypes indicate dispensable functions of Fgf4/8 and the possibility of redundancy among multiple Fgfs in GT development. Our results provide new insights into the integration of growth factor signaling in the appendicular developmental programs that regulate external genitalia development.

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Section: ;Ctnnb1mentioning

confidence: 99%

Dosage-dependent hedgehog signals integrated with Wnt/β-catenin signaling regulate external genitalia formation as an appendicular program

et al. 2009

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“…We show that this is not the case, because the muscle arrives to the vicinity of the orifices at embryonic day 14. The cloacal membrane perforates in mouse by E14.0 and the gross septation of the cloaca is completed by this stage (Hynes and Fraher, 2004). Thus, the connection with its contraleteral counterpart occurs after splitting into the single muscular primordia around the orifices.…”

Section: Cloacal Muscles Are Homologous To Perineal Musclesmentioning

confidence: 99%

A dual fate of the hindlimb muscle mass: cloacal/perineal musculature develops from leg muscle cells

et al. 2005

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The cloaca serves as a common opening to the urinary and digestive systems. In most mammals, the cloaca is present only during embryogenesis, after which it undergoes a series of septation events leading to the formation of the anal canal and parts of the urogenital tract. During embryogenesis it is surrounded by skeletal muscle. The origin and the mechanisms regulating the development of these muscles have never been determined. Here, we show that the cloacal muscles of the chick originate from somites 30-34, which overlap the domain that gives rise to leg muscles (somites 26-33). Using molecular and cell labelling protocols, we have determined the aetiology of cloacal muscles. Surprisingly, we found that chick cloacal myoblasts first migrate into the developing leg bud and then extend out of the ventral muscle mass towards the cloacal tubercle. The development of homologous cloacal/perineal muscles was also examined in the mouse. Concordant with the results in birds, we found that perineal muscles in mammals also develop from the ventral muscle mass of the hindlimb. We provide genetic evidence that the perineal muscles are migratory, like limb muscles, by showing that they are absent in metd/d mutants. Using experimental embryological procedures (in chick) and genetic models (in chick and mouse), we show that the development of the cloacal musculature is dependent on proximal leg field formation. Thus, we have discovered a novel developmental mechanism in vertebrates whereby muscle cells first migrate from axially located somites to the pelvic limb, then extend towards the midline and only then differentiate into the single cloacal/perineal muscles.

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“…Both the urogenital sinus and hindgut are initially joined as a single excretory tract at the embryonic cloaca. The subsequent division of the cloaca into separate urogenital and anorectal tracts occurs by 8 weeks of gestation in humans and 13.5 days post coitum (dpc) in the mouse (Hynes and Fraher, 2004); interestingly, this process has long been thought to occur by formation of a urorectal septum, but an alternative model has recently been proposed (Huang et al, 2016). The primitive urogenital sinus is then subdivided into the bladder at its rostral end, the urogenital sinus (UGS) in the middle, and the penile urethra caudally.…”

Section: Introductionmentioning

confidence: 99%

Prostate organogenesis: tissue induction, hormonal regulation and cell type specification

2017

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Prostate organogenesis is a complex process that is primarily mediated by the presence of androgens and subsequent mesenchyme-epithelial interactions. The investigation of prostate development is partly driven by its potential relevance to prostate cancer, in particular the apparent re-awakening of key developmental programs that occur during tumorigenesis. However, our current knowledge of the mechanisms that drive prostate organogenesis is far from complete. Here, we provide a comprehensive overview of prostate development, focusing on recent findings regarding sexual dimorphism, bud induction, branching morphogenesis and cellular differentiation.

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The development of the male genitourinary system. I. The origin of the urorectal septum and the formation of the perineum

Cited by 64 publications

References 16 publications

Dosage-dependent hedgehog signals integrated with Wnt/β-catenin signaling regulate external genitalia formation as an appendicular program

Dosage-dependent hedgehog signals integrated with Wnt/β-catenin signaling regulate external genitalia formation as an appendicular program

A dual fate of the hindlimb muscle mass: cloacal/perineal musculature develops from leg muscle cells

Prostate organogenesis: tissue induction, hormonal regulation and cell type specification

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