Molecular Characterization of the Genital Organizer: Gene Expression Profile of the Mouse Urethral Plate Epithelium

Armfield, Brooke A.; Seifert, Ashley W.; Zheng, Zhengui; Merton, Emily M.; Rock, Jason R.; Lopez, Maria-Cecilia; Baker, Henry V.; Cohn, Martin J.

doi:10.1016/j.juro.2016.04.091

Cited by 10 publications

(6 citation statements)

References 30 publications

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“…There is no doubt that urethral plate plays a central role in development of the penile urethra in both mice and humans (Cunha et al, 2015;Armfield et al, 2016). When initially formed at E12 in mice, the urethral plate extends to the distal portion of the genital tubercle (Hynes and Fraher, 2004a).…”

Section: Development Of the Human Penile Urethramentioning

confidence: 99%

“…Formation of the penile urethra has been studied in rodents with the tacit, but unproven, assumption that developmental processes in rodent models are relevant to human penile development. Clearly there are some developmental events shared between species such as the formation of a solid urethra plate within the embryonic genital tubercle (GT), which is observed in mouse, rat, rabbit, tamar wallaby, spotted hyena and human (Armfield et al, 2016;Li et al, 2015;Hynes and Fraher, 2004a;Kluth et al, 2011;Agras et al, 2006Agras et al, , 2007bAgras et al, , 2007aCunha et al, 2014;Butler et al, 1999;Kurzrock et al, 2000). Most of the mouse penile urethra forms by direct canalization of the urethral plate Fraher, 2004a, 2004b;Seifert et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

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Contrasting mechanisms of penile urethral formation in mouse and human

Liu

Shen

et al. 2018

Differentiation

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This paper addresses the developmental mechanisms of formation of the mouse and human penile urethra and the possibility that two disparate mechanisms are at play. It has been suggested that the entire penile urethra of the mouse forms via direct canalization of the endodermal urethral plate. While this mechanism surely accounts for development of the proximal portion of the mouse penile urethra, we suggest that the distal portion of the mouse penile urethra forms via a series of epithelial fusion events. Through review of the recent literature in combination with new data, it is unlikely that the entire mouse urethra is formed from the endodermal urethral plate due in part to the fact that from E14 onward the urethral plate is not present in the distal aspect of the genital tubercle. Formation of the distal portion of the mouse urethra receives substantial contribution from the preputial swellings that form the preputial-urethral groove and subsequently the preputial-urethral canal, the later of which is subdivided by a fusion event to form the distal portion of the mouse penile urethra. Examination of human penile development also reveals comparable dual morphogenetic mechanisms. However, in the case of human, direct canalization of the urethral plate occurs in the glans, while fusion events are involved in formation of the urethra within the penile shaft, a pattern exactly opposite to that of the mouse. The highest incidence of hypospadias in humans occurs at the junction of these two different developmental mechanisms. The relevance of the mouse as a model of human hypospadias is discussed.

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Section: Development Of the Human Penile Urethramentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Contrasting mechanisms of penile urethral formation in mouse and human

Liu

Shen

et al. 2018

Differentiation

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“…96 Other genes such as MID1, implicated in Opitz G/BBB syndrome, have been found mutated in patients with hypospadias. 97,98 Epidermal growth factor exhibits decreased expression in the tissue surrounding the urethral plate in hypospadiac boys but no mutations have been reported. 99 This may be an epiphenomenon of another cause.…”

Section: Other Genesmentioning

confidence: 99%

“…One way to identify new candidate genes is to compare the gene expression in urethral plates to that in unaffected tissues. Armfield et al showed that 89 genes exhibited a differential expression between urethral plate epithelium and surrounding tissue in mouse genital tubercles, 84 of them with a major hyper expression (×20) in the urethral endoderm. Subsequent in situ hybridizations confirmed for a subset of 54 genes that most of them were overexpressed in the urethral plate, thus providing meaningful candidates.…”

Section: Molecular Genetics Of Hypospadiasmentioning

confidence: 99%

Molecular genetics of hypospadias and cryptorchidism recent developments

et al. 2018

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During the last decade, a tremendous amount of work has been devoted to the study of the molecular genetics of isolated hypospadias and cryptorchidism, two minor forms of disorders of sex development (DSD). Beyond the genes involved in gonadal determination and sex differentiation, including those underlying androgen biosynthesis and signaling, new genes have been identified through genome-wide association study and familial clustering. Even if no single genetic defect can explain the whole spectrum of DSD, these recent studies reinforce the strong role of the genetic background in the occurrence of these defects. The timing of signaling disruption may explain the different phenotypes.

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“…Other in vivo models for analyzing urogenital tract development use the mouse genital tubercle and its associated reproductive structures [Armfield et al, 2016].…”

Section: Animal Models For the Discovery Of Gene Functionsmentioning

confidence: 99%

Development of Laboratory Investigations in Disorders of Sex Development

Audí

Camats²,

Fernández‐Cancio³

et al. 2017

Sex Dev

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Scientific knowledge to understand the biological basis of sex development was prompted by the observation of variants different from the 2 most frequent body types, and this became one of the fields first studied by modern pediatric endocrinology. The clinical observation was supported by professionals working in different areas of laboratory sciences which led to the description of adrenal and gonadal steroidogenesis, the enzymes involved, and the different deficiencies. Steroid hormone measurements evolved from colorimetry to radioimmunoassay (RIA) and automated immunoassays, although gas and liquid chromatography coupled to mass spectrometry are now the gold standard techniques for steroid measurements. Peptide hormones and growth factors were purified, and their measurement evolved from RIA to automated immunoassays. Hormone action mechanisms were described, and their specific receptors were characterized and assayed in experimental materials and in patient tissues and cell cultures. The discovery of the genetic basis for variant sex developments began with the description of the sex chromosomes. Molecular technology allowed cloning of genes coding for the different proteins involved in sex determination and development. Experimental animal models aided in verifying the roles of proteins and also suggested new genes to be investigated. New candidate genes continue to be described based on experimental models and on next-generation sequencing of patient DNAs.

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Molecular Characterization of the Genital Organizer: Gene Expression Profile of the Mouse Urethral Plate Epithelium

Cited by 10 publications

References 30 publications

Contrasting mechanisms of penile urethral formation in mouse and human

Contrasting mechanisms of penile urethral formation in mouse and human

Molecular genetics of hypospadias and cryptorchidism recent developments

Development of Laboratory Investigations in Disorders of Sex Development

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