Development of the amniote ventrolateral body wall.

In vertebrates, the trunk consists of the musculoskeletal structures of the back and the ventrolateral body wall, which together enclose the internal organs of the circulatory, digestive, respiratory and urogenital systems. This review gives an overview on the development of the thoracic and abdominal wall during amniote embryogenesis. Specifically, I briefly summarize relevant historical concepts and the present knowledge on the early embryonic development of ribs, sternum, intercostal muscles and abdominal muscles with respect to anatomical bauplan, origin and specification of precursor cells, initial steps of pattern formation, and cellular and molecular regulation of morphogenesis.

A Nomogram of Lateral Abdominal Wall Fat Thickness in Normal Third Trimester Fetuses.

OBJECTIVES: The objective of this study is to establish a nomogram of fetal abdominal wall fat thickness in fetuses with known normal neonatal outcomes. METHODS: After IRB approval (HSD-49496), 157 ultrasound examinations in 100 patients, 41 of whom had multiple examinations during the same pregnancy were reviewed. The thickness of the fetal lateral abdominal wall fat Interreader agreement was summarized using the intraclass correlation coefficient (ICC). Fat thickness growth curve equations were estimated to quantify the relationship between fat thickness and gestational age. RESULTS: The abdominal wall fat had an intraclass correlation coefficient of 0.93 (95% confidence interval, 0.90-0.96) for 2 readers. Fat thickness increased in all 41 fetuses with multiple examinations (P < 0.001). Fat thickness increased 0.19 mm per week on average (95% confidence interval, 0.17-0.21 mm; P < 0.001) from an average of 1.7 mm at 22 weeks and 4.3 mm at 36 weeks. CONCLUSIONS: Lateral wall abdominal fat can be reproducibly measured with good inter observer correlation, and fat does increase with increasing gestational age in normal fetuses. We believe the utility of fetal fat is the documentation of its presence as a reassuring finding indicative of normal fetal health, particularly when prior dating is discrepant or not available during the third trimester.

CHALLENGES AND MANAGEMENT OF CONGENITAL ABDOMINAL WALL DEFECTS (REVIEW).

Management of congenital abdominal wall malformations is still a challenge in paediatric surgery due to visceroabdominal disproportion, large defects of abdominal wall and immature abdominal cavity. Most of the patients treated with primary closure need artificial substitutes like patches or biomaterials for non-permanent abdominal wall closure. Patches represent the source of constant infections and complications like separation of prosthesis from fascia. Removal of these patches and ventral hernia repair is essential afterwards. As for component separation technique, this method helps to restore normal anatomy of anterior abdominal wall, results in good cosmetic appearance, requires only one-stage operation procedure, minimal skin flap advancement and is associated with lower infection risk. Although, while performing component separation technique, perforator branches of epigastric artery (periumbilical perforators) are damaged and puts the vascularization of the skin at the risk. Only pudendal artery branches and intercostal arteries are left to supply the skin with the blood, which from our point of view is insufficient. Accordingly, for successful treatment of congenital abdominal wall defects, further research in order to develop new operation techniques, as well as search for the ideal biomaterials for the closure of the large defects of anterior abdominal wall is essential. These biomaterials should possess unique biological properties that are important for tissue repair, including anti-inflammatory, antimicrobial, antifibrosis, antiscarring, as well as a reasonable cost and low immunogenicity.

Paradigm shift regarding the transversalis fascia, preperitoneal space, and Retzius' space.

BACKGROUND: There has been confusion in the anatomical recognition when performing inguinal hernia operations in Japan. From now on, a paradigm shift from the concept of two-dimensional layer structure to the three-dimensional space recognition is necessary to promote an understanding of anatomy. ANATOMY AND EMBRYOLOGY: Along with the formation of the abdominal wall, the extraperitoneal space is formed by the transversalis fascia and preperitoneal space. The transversalis fascia is a somatic vascular fascia originating from an arteriovenous fascia. It is a dense areolar tissue layer at the outermost of the extraperitoneal space that runs under the diaphragm and widely lines the body wall muscle. The umbilical funiculus is taken into the abdominal wall and transformed into the preperitoneal space that is a local three-dimensional cavity enveloping preperitoneal fasciae composed of the renal fascia, vesicohypogastric fascia, and testiculoeferential fascia. The Retzius' space is an artificial cavity formed at the boundary between the transversalis fascia and preperitoneal space. In the underlay mesh repair, the mesh expands in the range spanning across the Retzius' space and preperitoneal space.

Fetal Rat Gubernaculum Mesenchymal Cells Adopt Myogenic and Myofibroblast-Like Phenotypes.

PURPOSE: Gubernaculum-cremaster complex development is hormonally regulated and abnormal in a cryptorchid rat model. Using cell tracking techniques and imaging we studied myogenic phenotypes and fates in the fetal rat gubernaculum-cremaster complex. MATERIALS AND METHODS: Embryonic day 17 gubernaculum-cremaster complexes were labeled with CellTracker™ or the DNA synthesis marker EdU (5-ethynyl-2'-deoxyuridine), or immobilized in Matrigel® and grown in culture. Embryonic day 17 to 21 gubernaculum-cremaster complex sections and cells were imaged using wide field and deconvolution immunofluorescence microscopy, and muscle and/or myofibroblast specific antibodies. Deconvolved image stacks were used to create a 3-dimensional model of embryonic day 21 gubernaculum-cremaster complex muscle. RESULTS: PAX7 (paired box 7) positive and myogenin positive muscle precursors were visible in a desmin-rich myogenic zone between muscle layers that elongated and became thicker during development. Gubernaculum-cremaster complex inner mesenchymal cells expressed desmin and αSMA (α smooth muscle actin) at lower levels than in the myogenic zone. After pulse labeling with CellTracker or EdU mesenchymal cells became incorporated into differentiated muscle. Conversely, mesenchymal cells migrated beyond Matrigel immobilized gubernaculum-cremaster complexes, expressed PAX7 and fused to form striated myotubes. Mesenchymal gubernaculum-cremaster complex cell lines proliferated more than 40 passages and showed contractile behavior but did not form striated muscle. Our 3-dimensional gubernaculum-cremaster complex model had 2 orthogonal ventral layers and an arcing inner layer of muscle. CONCLUSIONS: Our data suggest that mesenchymal cells in the peripheral myogenic zone of the fetal gubernaculum-cremaster complex contribute to formation of a distinctively patterned cremaster muscle. Nonmyogenic, desmin and αSMA positive gubernaculum-cremaster complex mesenchymal cells proliferate and have a myofibroblast-like phenotype in culture. Intrinsic mechanical properties of these divergent cell types may facilitate perinatal inversion of the gubernaculum-cremaster complex.

Development of the ventral body wall in the human embryo.

Migratory failure of somitic cells is the commonest explanation for ventral body wall defects. However, the embryo increases ~ 25-fold in volume in the period that the ventral body wall forms, so that differential growth may, instead, account for the observed changes in topography. Human embryos between 4 and 10 weeks of development were studied, using amira reconstruction and cinema 4D remodeling software for visualization. Initially, vertebrae and ribs had formed medially, and primordia of sternum and hypaxial flank muscle primordium laterally in the body wall at Carnegie Stage (CS)15 (5.5 weeks). The next week, ribs and muscle primordium expanded in ventrolateral direction only. At CS18 (6.5 weeks), separate intercostal and abdominal wall muscles differentiated, and ribs, sterna, and muscles began to expand ventromedially and caudally, with the bilateral sternal bars fusing in the midline after CS20 (7 weeks) and the rectus muscles reaching the umbilicus at CS23 (8 weeks). The near-constant absolute distance between both rectus muscles and approximately fivefold decline of this distance relative to body circumference between 6 and 10 weeks identified dorsoventral growth in the dorsal body wall as determinant of the 'closure' of the ventral body wall. Concomitant with the straightening of the embryonic body axis after the 6th week, the abdominal muscles expanded ventrally and caudally to form the infraumbilical body wall. Our data, therefore, show that the ventral body wall is formed by differential dorsoventral growth in the dorsal part of the body.

Development of the annelid axochord: insights into notochord evolution.

The origin of chordates has been debated for more than a century, with one key issue being the emergence of the notochord. In vertebrates, the notochord develops by convergence and extension of the chordamesoderm, a population of midline cells of unique molecular identity. We identify a population of mesodermal cells in a developing invertebrate, the marine annelid Platynereis dumerilii, that converges and extends toward the midline and expresses a notochord-specific combination of genes. These cells differentiate into a longitudinal muscle, the axochord, that is positioned between central nervous system and axial blood vessel and secretes a strong collagenous extracellular matrix. Ancestral state reconstruction suggests that contractile mesodermal midline cells existed in bilaterian ancestors. We propose that these cells, via vacuolization and stiffening, gave rise to the chordate notochord.

Muscle patterning in mouse and human abdominal wall development and omphalocele specimens of humans.

Human omphalocele is a congenital defect of the abdominal wall in which the secondary abdominal wall structures (muscle and connective tissue) in an area centered around the umbilicus are replaced by a translucent membranous layer of tissue. Histological examination of omphalocele development and moreover the staging of normal human abdominal wall development has never been described. We hypothesized that omphalocele is the result of an arrest in the secondary abdominal wall development and predicted that we would observe delays in myoblast maturation and an arrest in secondary abdominal wall development. To look for evidence in support of our hypothesis, we performed a histological analysis of normal human abdominal wall development and compared this to mouse. We also conducted the first histological analysis of two human specimens with omphalocele. In these two omphalocele specimens, secondary abdominal wall development appears to have undergone an arrest around Carnegie Stage 19. In both specimens disruptions in the unidirectional orientation of myofibers were observed in the external and internal obliques, and rectus abdominis but not in the transversus abdominis. These latter findings support a model of normal abdominal wall development in which positional information instructs the orientation of myoblasts as they organize into individual muscle groups.

Conditional mutation of fibroblast growth factor receptors 1 and 2 results in an omphalocele in mice associated with disruptions in ventral body wall muscle formation.

BACKGROUND/PURPOSE: We observed that fibroblast growth factor receptors 1 and 2 (Fgfr1, Fgfr2) are expressed during abdominal wall development in mice and hypothesized that conditional mutation of these genes would result in abdominal wall defects. METHODS: Section in situ hybridizations were performed for Fgfr1 and Fgfr2 on wild-type embryos at embryonic day (E) 11.5 and E13.5. Conditional mutation of Fgfr1and Fgfr2 was achieved with a tamoxifen inducible Cre at E8.5. Litters were harvested at E17.5, whole mount photographs were taken, and paraffin sections were generated and stained with hematoxylin and eosin. RESULTS: Fgfr1 was expressed in ectoderm, lateral plate mesoderm, and myoblasts, whereas Fgfr2 was expressed almost exclusively in the early dermis and ectoderm of the abdominal wall. Conditional mutation of both Fgfr2 alleles and one Fgfr1 allele resulted in omphalocele in 38.7% of mutants. Histologic examination in mutants demonstrated disruptions in dermal and muscle development. CONCLUSIONS: Mutant embryos with omphalocele arising from mutation in Fgfr1 and Fgfr2 exhibit disruptions in the development of the secondary abdominal wall structures. These findings are consistent with a model of ventral abdominal wall development in which organization of the muscles and connective tissue (secondary abdominal wall structures) is influenced by positional information emanating from the primary abdominal wall.

Inguinal canal development: the muscular wall and the role of the gubernaculum.

The inguinal canal is an anatomically complex region. Although much has been written about the gubernaculum and the descent of the testis, little is known about the development of the abdominal wall itself. We dissected this inguinal canal in 75 fetuses between 10 and 25 weeks of gestation, 42 males and 33 females. We identified the anterior body-wall muscular layers, located the gonads and uterus, and observed the formation of the scrotum. The gubernaculum was dissected, from the deep to the superficial ends and its distal attachments were determined. We proved that the muscular-fibrous layers of the wall were well-differentiated and observed how the inguinal canal enlarged with embryological development. In only one of the cases, an abnormal testis was found located in the scrotum. The upper end of the gubernaculum inserted into the inferior pole of the testis or the lateral angle of the uterus, according to gender. The lower end was attached by one or multiple tails, mainly on the pubic bone. This fact explained the clinical findings of ectopic testis. Observations of the abdominal wall and its relationship with the gubernaculum assisted us in explaining the development of the inguinal region, the formation of the inguinal canal, and the presence of the gubernaculum, in both genders. We intend to explain how the deep inguinal ring moves upwards, bringing the gubernaculum along with it, and thus determines the final form of the inguinal canal.

Delayed synaptic transmission in Drosophila cacophonynull embryos.

Ca(2+) influx through the Drosophila N-type Ca(2+) channel, encoded by cacophony (cac), triggers fast synaptic transmission. We now ask whether the cac Ca(2+) channel is the Ca(2+) channel solely dedicated for fast synaptic transmission. Because the cac(null) mutation is lethal, we used cac(null) embryos to address this question. At the neuromuscular junction in HL3 solution, no fast synchronous synaptic transmission was detected on nerve stimulation. When the wild-type cac gene was introduced in the cac(null) background, fast synaptic transmission recovered. However, even in cac(null) embryos, nerve stimulation infrequently induced delayed synaptic events in the minority of cells in 1.5 mM [Ca(2+)](e) and in the majority of cells in 5 mM [Ca(2+)](e). The number of delayed quantal events per stimulus was greater in 5 mM [Ca(2+)](e) than in 1.5 mM. Thus the delayed release is [Ca(2+)](e) dependent. Plectreurys toxin II (PLTXII) (10 nM; a spider toxin analog) depressed the frequency of delayed events, suggesting that voltage-gated Ca(2+) channels, other than cac Ca(2+) channels, are contributing to them. However, delayed events were not affected by 50 microM La(3+). The frequency of miniature synaptic currents in cac(null) embryos was approximately 1/2 of control, whereas in high K(+) solutions, it was approximately 1/135. The hypertonicity response was approximately 1/10 of control. These findings indicate that the number of release-ready vesicles is smaller in cac(null) embryos. Taken together, the cac Ca(2+) channel is indispensable for fast synaptic transmission in normal conditions, and another type of Ca(2+) channel, the non-cac, PLTXII-sensitive Ca(2+) channel, is contributing to delayed release in cac(null) embryos.

Development of the diaphragm and genetic mouse models of diaphragmatic defects.

Improving our understanding of diaphragmatic development is essential to making progress in defining the pathogenesis and genetic etiologies of congenital diaphragmatic defects in humans. As mouse genetic technology has given us new tools to manipulate and observe development, a number of mouse models have recently emerged that provide valuable insight to this field. In this article, we review our current understanding of diaphragmatic embryogenesis including the origin of diaphragmatic tissue. We use rodent models to review the muscularization of the diaphragm and review selected genetic models of abnormal muscularization. We also review models of posterior diaphragmatic defects and discuss evidence for the pleuroperitoneal fold (PPF) tissue contributing to the diaphragm. Finally, we discuss models of anterior and central hernias. It may be simplistic to subdivide this review based on anatomic regions of the diaphragm, as evidence is emerging that defects in different regions of the diaphragm in humans and in mice may be etiologically related. However, at this time we do not have enough knowledge to make more mechanistic or genetic classifications though with time, genetic progress in the field of diaphragm development will allow us to do this.

Spigelian hernia: surgical anatomy, embryology, and technique of repair.

Spigelian hernia (1-2% of all hernias) is the protrusion of preperitoneal fat, peritoneal sac, or organ(s) through a congenital or acquired defect in the spigelian aponeurosis (i.e., the aponeurosis of the transverse abdominal muscle limited by the linea semilunaris laterally and the lateral edge of the rectus muscle medially). Mostly, these hernias lie in the "spigelian hernia belt," a transverse 6-cm-wide zone above the interspinal plane; lower hernias are rare and should be differentiated from direct inguinal or supravescical hernias. Although named after Adriaan van der Spieghel, he only described the semilunar line (linea Spigeli) in 1645. Josef Klinkosch in 1764 first defined the spigelian hernia as a defect in the semilunar line. Defects in the aponeurosis of transverse abdominal muscle (mainly under the arcuate line and more often in obese individuals) have been considered as the principal etiologic factor. Pediatric cases, especially neonates and infants, are mostly congenital. Embryologically, spigelian hernias may represent the clinical outcome of weak areas in the continuation of aponeuroses of layered abdominal muscles as they develop separately in the mesenchyme of the somatopleura, originating from the invading and fusing myotomes. Traditionally, repair consists of open anterior herniorraphy, using direct muscle approximation, mesh, and prostheses. Laparoscopy, preferably a totally extraperitoneal procedure, or intraperitoneal when other surgical repairs are planned within the same procedure, is currently employed as an adjunct to diagnosis and treatment of spigelian hernias. Care must be taken not to create iatrogenic spigelian hernias when using laparoscopy trocars or classic drains in the spigelian aponeurosis.

Limb-body wall complex: a compound anomaly pattern in body-wall defects.

Our presentation of four cases demonstrates the essential features of limb-body wall complex (LBWC), representing a compound anomaly pattern in body-wall defects. The diagnosis of this entity is based on two of the three following characteristics: (1) exencephaly/encephalocele and facial clefts; (2) thoraco- and/or abdominoschisis; and (3) limb defects. A definite association with internal anomalies and severe kyphoscoliosis makes a more distinct concept of the pathogenesis reasonable. Limb-body wall malformations result from a malfunction of the ectodermal placodes involving the early embryonic folding process. The poor prognosis of LBWC calls for early antenatal diagnosis.

Impaired abdominal wall development and deficient wound healing in mice lacking aortic carboxypeptidase-like protein.

Aortic carboxypeptidase-like protein (ACLP) is a member of a diverse group of proteins that contain a domain with similarity to that of the Dictyostelium discoideum protein discoidin I. The discoidin domain has been identified in mammalian milk fat globule membrane proteins, blood coagulation factors, and receptor tyrosine kinases, where it may facilitate cell aggregation, adhesion, or cell-cell recognition. Here we show that ACLP is a secreted protein that associates with the extracellular matrix (ECM). During mouse embryogenesis, ACLP is abundantly expressed in the ECM of collagen-rich tissues, including the vasculature, dermis, and the developing skeleton. We deleted the ACLP gene in mice by homologous recombination. The majority of ACLP(-/-) mice die perinatally due to gastroschisis, a severe disruption of the anterior abdominal wall and herniation of the abdominal organs. ACLP(-/-) mice that survived to adulthood developed nonhealing skin wounds. Following injury by a dermal punch biopsy, ACLP(-/-) mice exhibited deficient wound healing compared with controls. In addition, dermal fibroblasts isolated from ACLP(-/-) 18.5-day-postconception embryos exhibited a reduced proliferative capacity compared with wild-type cells. These results indicate that ACLP is an ECM protein that is essential for embryonic development and dermal wound healing processes.

Embryology, anatomy, and surgical applications of the preperitoneal space.

The preperitoneal space is presented from an embryologic, anatomic, and surgical standpoint in detail. Because this space is one of the most used areas for the repair of groin hernias, knowledge of its embryology and anatomy is essential.

A new photogrammetric method to measure fetal breathing movements.

OBJECTIVE: In most recent studies, fetal respiratory movements have been measured with real-time and Doppler echography. We describe an alternative approach using photogrammetry that provides more objective measurements. METHODS: Respiratory movements were studied in 28 women with uncomplicated pregnancies of 30-38 weeks' gestation. Fetal echographic images were recorded on videotape and digitized to obtain coordinates of the reference point (midpoint on the anterior abdominal wall of the fetus between the xiphoid process and the insertion of the umbilical vessels) and generate graphic representations of fetal movements in the anterior abdomen. RESULTS: The mean duration of a complete respiratory cycle was 1.194 s, the mean distance representing the extent of movement was 2.92 mm, the mean inspiratory velocity was 5.52 mm/s and the mean expiratory velocity was 5.06 mm/s. CONCLUSIONS: Photogrammetric analysis of images obtained with real-time echography provided accurate measurements of fetal breathing movements.

Screening for fetal abdominal wall defects.

Failure of the lateral ventral folds to close by the third month of embryonic life results in an omphalocele. Although the abdominal wall defect is easily closed, the survival rate for infants with an omphalocele remains only 79%, largely the result of coexistent anomalies and chromosomal abnormalities. Gastroschisis is a deformation caused by disruption of the right omphalomesenteric artery and a resultant full-thickness defect in the abdominal wall. As a result, small bowel and, on occasion, even large bowel herniate into the amniotic space. Despite evidence of increased bowel irritability manifested by echogenic bowel wall thickening in fetuses with gastroschisis, the survival rate of more than 95% is largely the result of the lack of other severe anomalies associated with this defect. In addition, recent evidence suggests that the improvement in survival rate is also the result of improved perinatal care. The ability of perinatal specialists to categorize the defect along with associated anomalies and improved counseling regarding neonatal outcome have measurably increased the ability of families to assess the reproductive consequences and make informed decisions. This article outlines methods to identify patients at risk for having a fetus with an abdominal wall defect along with sonographic techniques to diagnose the majority of cases. Prompt consultation with individuals skilled in evaluating such defects ensures that appropriate perinatal care is provided.

A locus for radiation-induced gastroschisis on mouse Chromosome 7.

Gastroschisis (abdominal wall defects) occurs with a high frequency in the mouse inbred strain HLG compared with C57BL/6J mice. The risk of gastroschisis increases significantly after exposure to irradiation with X-rays during preimplantation development and follows a recessive mode of inheritance for the HLG susceptibility alleles. We have used a backcross strategy and genome-wide microsatellite typing to chromosomally map this trait. A suggestive linkage for a locus responsible for radiation-induced gastroschisis (Rigs1) was found in a region of mouse Chromosome 7.