Six1 and Eya1 are critical regulators of peri-cloacal mesenchymal progenitors during genitourinary tract development

Wang, Chen; Gargollo, Patricio C.; Guo, Caiwei; Tang, Tielong; Mingin, Gerald C.; Sun, Ye; Li, Xue

doi:10.1016/j.ydbio.2011.09.020

Cited by 36 publications

(52 citation statements)

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“…For example, the transcription factors Six1 and Six2 , which are asymmetrically expressed in the mesenchyme surrounding the embryonic cloaca, are required for the genitourinary tract formation including cloaca septation 37;38 . This asymmetrical expression has been suggested to create an unbalanced growth of the mesenchyme which turns out to be the driving force that separates the cloaca 38 .…”

Section: Signaling Pathways Involved In Cloaca Malformationsmentioning

confidence: 99%

“…The cloaca mesenchymal cells have been considered to be essential in the differentiation process 1;7;8 . These mesenchymal cells express intrinsic regulators crucial during genitourinary tract formation, including cloacal separation 9 . A proper balance of epithelial cell death called apoptosis, cell growth, and maturation is needed in the process of cloaca separation.…”

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confidence: 99%

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The great divide: septation and malformation of the cloaca, and its implications for surgeons

et al. 2014

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The anorectal and urogenital systems arise from a common embryonic structure termed cloaca. Subsequent development leads to the division/septation of the cloaca into the urethra, urinary bladder, vagina, anal canal, and rectum. Defective cloacal development and the resulting anorectal and urogenital malformations are some of the most severe congenital anomalies encountered in children. In the most severe form in females, the rectum, vagina, and urethra fail to develop separately and drain via a single common channel known as a cloaca into the perineum. In this review, we summarize our current knowledge of embryonic cloaca development and malformation, and compare them to what has already been described in literature. We describe the use of mouse models of cloaca malformation to understand which signaling pathways and cellular mechanisms are involved in the process of normal cloaca development. We also discuss the embryological correlation of the epithelial and stromal histology found in step sections of the common channel in fourteen human cloaca malformations. Finally, we highlight the significance of these findings, compare them to prior studies, and discuss their implications for the pediatric surgeons. Understanding and identifying the molecular basis for cloaca malformation could provide foundation for tissue engineering efforts that in the future would reflect better surgical reconstruction and improved quality of life for patients.

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Section: Signaling Pathways Involved In Cloaca Malformationsmentioning

confidence: 99%

mentioning

confidence: 99%

The great divide: septation and malformation of the cloaca, and its implications for surgeons

et al. 2014

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“…3; Baskin et al, 2004;Seifert et al, 2008;Wang et al, 2011;Guo et al, 2014). At E17, the GT has differentiated sufficiently to be recognised as the penis/clitoris, and the PHUR becomes the penile urethra in males.…”

Section: Introductionmentioning

confidence: 99%

An illustrated anatomical ontology of the developing mouse lower urogenital tract

et al. 2015

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Malformation of the urogenital tract represents a considerable paediatric burden, with many defects affecting the lower urinary tract (LUT), genital tubercle and associated structures. Understanding the molecular basis of such defects frequently draws on murine models. However, human anatomical terms do not always superimpose on the mouse, and the lack of accurate and standardised nomenclature is hampering the utility of such animal models. We previously developed an anatomical ontology for the murine urogenital system. Here, we present a comprehensive update of this ontology pertaining to mouse LUT, genital tubercle and associated reproductive structures (E10.5 to adult). Ontology changes were based on recently published insights into the cellular and gross anatomy of these structures, and on new analyses of epithelial cell types present in the pelvic urethra and regions of the bladder. Ontology changes include new structures, tissue layers and cell types within the LUT, external genitalia and lower reproductive structures. Representative illustrations, detailed text descriptions and molecular markers that selectively label muscle, nerves/ganglia and epithelia of the lower urogenital system are also presented. The revised ontology will be an important tool for researchers studying urogenital development/malformation in mouse models and will improve our capacity to appropriately interpret these with respect to the human situation.

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“…Six1 and Eya1 mutants displayed GT hypoplasia and hypospadiaslike phenotypes. Interestingly, Six1:Eya1 compound mutants also show a decreased cell proliferation and increased apoptosis [Wang et al, 2011[Wang et al, , 2013 which is accompanied with upregulation of BMP signaling. It has been reported that augmented BMP signaling can reduce FGF8 and WNT5A expression and increase apoptosis [Suzuki et al, 2003].…”

Section: Development Of the Bipotential External Genitaliamentioning

confidence: 99%

“…This suggests that septation or the movement of URS into the base of the GT could be regulated by masculinizing factors. Additionally, the PCM is also reported to contribute to the perineum [Wang et al, 2011]. Hence, proper morphogenesis of the PCM is also a requirement for perineum formation, but its sexually dimorphic aspect is not yet investigated.…”

Section: Sexual Dimorphism During External Genitalia Development: Mormentioning

confidence: 99%

Development of the External Genitalia and Their Sexual Dimorphic Regulation in Mice

Ipulan¹,

Suzuki²,

Matsushita³

et al. 2014

Sex Dev

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The study of the external genitalia is divided into 2 developmental stages: the formation and growth of a bipotential genital tubercle (GT) and the sexual differentiation of the male and female GT. The sexually dimorphic processes, which occur during the second part of GT differentiation, are suggested to be governed by androgen signaling and more recently crosstalk with other signaling factors. The process of elucidating the regulatory mechanisms of hormone signaling towards other signaling networks in the GT is still in its early stages. Nevertheless, it is becoming a productive area of research. This review summarizes various studies on the development of the murine GT and the defining characteristics of a masculinized GT and presents the different signaling pathways possibly involved during masculinization.

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Six1 and Eya1 are critical regulators of peri-cloacal mesenchymal progenitors during genitourinary tract development

Cited by 36 publications

References 50 publications

The great divide: septation and malformation of the cloaca, and its implications for surgeons

The great divide: septation and malformation of the cloaca, and its implications for surgeons

An illustrated anatomical ontology of the developing mouse lower urogenital tract

Development of the External Genitalia and Their Sexual Dimorphic Regulation in Mice

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