Severe lower limb defects in exstrophy of the cloaca

Jain, Mahim; Weaver, David D.

doi:10.1002/ajmg.a.30103

Cited by 20 publications

(11 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Intriguingly, a recent study in the mouse has shown that a loss of Bmp7 combined with a half dose or complete loss of twisted gastrulation (Tsg) results in sirenomelia (Zakin et al, 2005). Bmp signaling defects in caudal mesoderm have been implicated by clinical researchers as one possible cause of analogous human malformations (Jain and Weaver, 2004). Zebrafish develop a ventral tail fin instead of a true set of hindlimbs, and loss of the ventral tail fin has been regarded as a readout for defects in ventral/caudal mesoderm (Tucker and Slack, 2004).…”

Section: Bmp Signaling and Human Developmental Defectsmentioning

confidence: 99%

Sustained Bmp signaling is essential for cloaca development in zebrafish

et al. 2006

View full text Add to dashboard Cite

Bone morphogenetic protein (Bmp) signaling has long been known to be important for the early development of the ventral mesoderm, including blood, vasculature and kidney cells. Although Bmp genes are continually expressed in the ventral cells throughout gastrulation and somitogenesis, previous studies in zebrafish have not addressed how the role of Bmp signaling changes over time to regulate ventral mesoderm development. Here, we describe the use of a transgenic inducible dominantnegative Bmp receptor line to examine the temporal roles of Bmp signaling in ventral mesoderm patterning. Surprisingly, we find that Bmp signaling from the mid-gastrula stage through early somitogenesis is important for excluding blood and vascular precursors from the extreme ventral mesoderm, and we show that this domain is normally required for development of the cloaca (the common gut and urogenital opening). Using a novel assay for cloacal function, we find that larvae with reduced mid-gastrula Bmp signaling cannot properly excrete waste. We show that the cloacal defects result from alterations in the morphogenesis of the cloaca and from changes in the expression of genes marking the excretory system. Finally, we show that HrT, a T-box transcription factor, is a Bmp-regulated gene that has an essential function in cloacal development. We conclude that sustained Bmp signaling plays an important role in specification of the zebrafish cloaca by maintaining the fate of extreme ventral cells during the course of gastrulation and early somitogenesis. Furthermore, our data suggest that alterations in Bmp signaling are one possible cause of anorectal malformations during human embryogenesis.

show abstract

Section: Bmp Signaling and Human Developmental Defectsmentioning

confidence: 99%

Sustained Bmp signaling is essential for cloaca development in zebrafish

et al. 2006

View full text Add to dashboard Cite

show abstract

“…Cloacal exstrophy with hindlimb defects may be related to abnormalities in the caudal mesoderm [32]. Because these defects often involve the more posterior parts of the body, some studies proposed that the cloacal defects induce several caudal defects including the most extreme form, namely caudal regression syndrome (CRS) [33].…”

Section: Introductionmentioning

confidence: 99%

New horizons at the caudal embryos: coordinated urogenital/reproductive organ formation by growth factor signaling

Suzuki

Economides

Yanagita

et al. 2009

Current Opinion in Genetics & Development

View full text Add to dashboard Cite

SummaryThe cloaca/urogenital sinus and its adjacent region differentiate into the urogenital/reproductive organs. Caudal regression syndrome (CRS; including Mermaid syndrome), a type of severe cloacal malformation displays hindlimb fusion and urogenital organ defects, thus suggesting that such defects are caused by several morphogenetic alterations during early development. The attenuation of Bone Morphogenetic Protein (Bmp) signaling at the posterior primitive streak of embryos leads to the caudal dysmorphogenesis including the cloaca and fusion of both hindlimbs. Genetic tissue lineage studies indicate the presence of coordinated organogenesis. Hedgehog (HH)-responding cells derived from peri-cloacal mesenchyme (PCM) contribute to the urogenital/reproductive organs. These findings indicate the existence o f developmental programs for the coordinated organogenesis of urogenital/reproductive tissues based on growth factor function and crosstalk.

show abstract

“…A higher tendency towards side-to-side asymmetry is also observed [43]. A review of the literature by Jain and Weaver revealed an incidence of lower limb abnormality in 17e26% of patients with cloacal exstrophy [44]. Certain limb malformations like club foot and equinovarus deformities can be associated with myelomeningocele, which often accompanies cloacal exstrophy; however, a variety of true limb malformations including hypoplasia, absence, split foot and ectopic additional digits, have also been observed [44].…”

Section: Skeletalmentioning

confidence: 89%

“…A review of the literature by Jain and Weaver revealed an incidence of lower limb abnormality in 17e26% of patients with cloacal exstrophy [44]. Certain limb malformations like club foot and equinovarus deformities can be associated with myelomeningocele, which often accompanies cloacal exstrophy; however, a variety of true limb malformations including hypoplasia, absence, split foot and ectopic additional digits, have also been observed [44]. Given the mesodermal origin of internal limb structures, it is postulated that mesodermal deficiency in the caudal region of the developing embryo is the common underlying abnormality [44].…”

Section: Skeletalmentioning

confidence: 98%