Urethral seam formation and hypospadias

Baskin, Laurence S.; Erol, Ali; Jegatheesan, Priya; Li, Yingwu; Liu, Wenhui; Cunha, Gerald R.

doi:10.1007/s004410000345

Cited by 120 publications

(104 citation statements)

References 19 publications

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“…Later, a UF develops further toward the midline and finally fuses in the midline to generate the tubular penile urethra 1 and the progressive formation of the UF leading to midline fusion from proximal to distal regions of the GT has been reported. 4 Within the GT, we have identified a transient epithelial structure located at the distal end of UP termed distal urethral epithelia (DUE). 5,6 The DUE expresses several growth factors, including Fgf (fibroblast growth factor), Bmps (bone morphogenetic proteins) and Sonic hedgehog (Shh).…”

Section: Introductionmentioning

confidence: 99%

Abnormal urethra formation in mouse models of Split-hand/split-foot malformation type 1 and type 4

et al. 2007

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Urogenital birth defects are one of the common phenotypes observed in hereditary human disorders. In particular, limb malformations are often associated with urogenital developmental abnormalities, as the case for Hand -foot -genital syndrome displaying similar hypoplasia/agenesis of limbs and external genitalia. Split-hand/split-foot malformation (SHFM) is a syndromic limb disorder affecting the central rays of the autopod with median clefts of the hands and feet, missing central fingers and often fusion of the remaining ones. SHFM type 1 (SHFM1) is linked to genomic deletions or rearrangements, which includes the distal-less-related homeogenes DLX5 and DLX6 as well as DSS1. SHFM type 4 (SHFM4) is associated with mutations in p63, which encodes a p53-related transcription factor. To understand that SHFM is associated with urogenital birth defects, we performed gene expression analysis and gene knockout mouse model analyses. We show here that Dlx5, Dlx6, p63 and Bmp7, one of the p63 downstream candidate genes, are all expressed in the developing urethral plate (UP) and that targeted inactivation of these genes in the mouse results in UP defects leading to abnormal urethra formation. These results suggested that different set of transcription factors and growth factor genes play similar developmental functions during embryonic urethra formation. Human SHFM syndromes display multiple phenotypes with variations in addition to split hand foot limb phenotype. These results suggest that different genes associated with human SHFM could also be involved in the aetiogenesis of hypospadias pointing toward a common molecular origin of these congenital malformations.

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Section: Introductionmentioning

confidence: 99%

Abnormal urethra formation in mouse models of Split-hand/split-foot malformation type 1 and type 4

et al. 2007

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“…Because of the presence of TUNEL-negative stratified epithelium (e.g., Figs. 7 and 8 in Baskin et al 2001), the usual type of apoptosis with DNA fragmentation seemed unlikely to occur in the present sc9758-positive sites. Therefore, we hypoth- esized that sc9758 cross-reacted with epithelium-related substances produced by the death process.…”

Section: Discussionmentioning

confidence: 55%

“…The preputial lamella also undergoes luminization to free the prepuce from the glans of the penis or clitoris. Notably, according to figures presented by Baskin et al (2001), the TUNEL method did not demonstrate any apoptotic cells in the preputial lamella of fetal mice. An epithelial plug has also been reported in the human fetal anal orifice (Nievelstein et al 1998).…”

Section: Introductionmentioning

confidence: 74%

“…These sites were commonly characterized by a specific stratified squamous epithelium composed of round or oval, enlarged cells with pale-staining cytoplasm and non-pyknotic nuclei. In the perineal region, the sc9758-positive sites did not include the so-called urethral seam, in which apoptosis can be identified using the TUNEL method (Baskin et al 2001). Because of the presence of TUNEL-negative stratified epithelium (e.g., Figs.…”

Section: Discussionmentioning

confidence: 99%

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False positive reactivity of a substance P-antibody in the ectodermal/epithelial plug of the nose, ear, eye and perineum of the human and mouse fetuses

Masumoto

Katori

Kawase

et al. 2010

Okajimas Folia Anat. Jpn.

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Summary:The main aim of this review is (1) to introduce the two previous studies we published human lower limb anatomy based on the conventional macroscopic anatomical criteria with hazardous recognition of this description, (2) to activate the discussion whether the limb homology exists, and (3) to contribute to future study filling the gap between the gross anatomy and embryology.One of the topic we discussed was the human persistent sciatic artery. To date, numerous human cases of persistent sciatic artery have been reported in which the anomalous artery was present in the posterior compartment of the thigh alongside the sciatic nerve. As one of the important criteria for assessing the human primitive sciatic artery, its ventral arterial position with respect to the sciatic nerve is reasonable based on the initial positional relationship between ventral arterial and dorsal nervous system and comparative anatomical findings. We also discuss ways of considering the topography of muscles of the lower limb and their innervations compared to those of the upper limb. We propose a schema of the complex anatomical characteristics of the lower limb based on the vertebrate body plan. According to this reasonable schema, the twisted anatomy of the lower limb can be understood more easily.These two main ideas discussed in this paper will be useful for further understanding of the anatomy of the lower limb and as a sirst step for future. We hope that the future study in lower limb will be further developed by both viewpoints of the classical gross anatomy and recent embryology.

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“…Failed seam formation during fusion of the urethral folds between fetal weeks 8 and 16 result in hypospadias. 7 Any gene having a role during the development of urogenital organs in the critical period is therefore a candidate gene for hypospadias. Mutations in the MID1 gene cause the X-linked form of Opitz G/BBB syndrome (OS, characterized by midline abnormalities such as hypertelorism, cleft lip/palate, tracheo-esophageal abnormalities, cardiac defects and hypospadias).…”

Section: Introductionmentioning

confidence: 99%

Hypospadias associated with hypertelorism, the mildest phenotype of Opitz syndrome

et al. 2011

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Hypospadias is a common congenital malformation in boys in which the urethral meatus opens on the underside of the penis. It is considered a complex disorder with several genes involved and the molecular etiology is just beginning to be revealed. As more than 85% of Opitz G/BBB syndrome (OS) patients with MID1 mutations are manifested with hypospadias, we have investigated the association between the MID1 gene and hypospadias. DNA from 114 hypospadias cases was analyzed with direct sequencing of the MID1 gene. Genotyping analysis was performed for the single-nucleotide polymorphism (SNP) c.1230G4A in 370 individuals with varying degrees of hypospadias and compared with 759 healthy controls. We identified one nonsense mutation c.712G4T (p.E238X), one missense mutation c.1679A4G (p.K560R) and two synonymous variants c.1230G4A (p.S410S) and c.1284T4G (p.V428V). We also detected a significant difference in the rare allele frequency of SNP c.1230G4A in hypospadias patients as compared with controls (P¼0.016). Our finding suggests that hypospadias associated with hypertelorism is the mildest phenotype in OS caused by MID1 mutations.

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Urethral seam formation and hypospadias

Cited by 120 publications

References 19 publications

Abnormal urethra formation in mouse models of Split-hand/split-foot malformation type 1 and type 4

Abnormal urethra formation in mouse models of Split-hand/split-foot malformation type 1 and type 4

False positive reactivity of a substance P-antibody in the ectodermal/epithelial plug of the nose, ear, eye and perineum of the human and mouse fetuses

Hypospadias associated with hypertelorism, the mildest phenotype of Opitz syndrome

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