Application of the mouse <i>exo utero</i> development system in the study of developmental biology and teratology

Hatta, Toshihisa; Matsumoto, Akihiro; Otani, Hiroki

doi:10.1111/j.1741-4520.2003.00002.x

Cited by 20 publications

(31 citation statements)

References 31 publications

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“…After the operation, the fetuses together with the uterus were placed back in the abdominal cavity of the dam, and the incision on the abdominal muscle was sutured closed with 3-or 4-0 silk line; incision of the abdominal skin was closed by autosuture (MikRon 9 mm Autoclip Applier), and were allowed to develop exo utero till E18.5. As in our several previous studies (Hatta et al, 1994(Hatta et al, , 2002(Hatta et al, , 2004Habib et al, 2005Habib et al, , 2007Jahan et al, 2010), we observed that the exo utero surgery as described caused no general growth retardation, and neither the CRL, BW, nor the mandibular morphology of the E18.5 sham-operated fetuses were significantly different from those of the E18.5 in utero normal fetuses. Therefore, we here show only the results of sham-operated fetuses, and not those of in utero normal fetuses, as the control.…”

Section: Exo Utero Surgery Of Mouse Fetuses To Restrict Temporomandibsupporting

confidence: 84%

Mathematical Analysis of Mandibular Morphogenesis by Micro‐CT‐Based Mouse and Alizarin Red S‐Stained‐Based Human Studies During Development

Rafiq

Udagawa

Lundh

et al. 2011

The Anatomical Record

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Prenatal development of the mandible is an important factor in its postnatal function. To examine quantitatively normal and abnormal developmental changes of the mandible, we here evaluated morphological changes in mineralizing mandibles by thin-plate spline (TPS) including bending energy (BE) and Procrustes distance (PD), and by Procrustes analyses including warp analysis, regression analysis, and discriminant function analysis. BE and PD were calculated from lateral views of the mandibles of mice or of human fetuses using scanned micro-computed tomography (CT) images or alizarin red S-stained specimens, respectively. BE and PD were compared (1) between different developmental stages, and further, to detect abnormalities in the data sets and to evaluate the deviation from normal development in mouse fetuses, (2) at embryonic day (E) 18.5 between the normal and deformed mandibles, the latter being caused by suturing the jaw at E15.5, (3) at E15.5 and E18.5 between normal and knockout mutant mice of receptor tyrosine kinaselike orphan receptor (Ror) 2. In mice, BE and PD were large during the prenatal period and small after postnatal day 3, suggesting that the mandibular shape changes rapidly during the prenatal and early postnatal periods. In humans, BE of the mandibles peaked at 16-19 weeks of gestation, suggesting the time-dependent change in the mandibular shape. TPS and Procrustes analyses statistically separated the abnormal mandibles of the sutured or Ror2 mutant mouse fetuses from the normal mandible. These results suggest that TPS and Procrustes analyses are useful for assessing the morphogenesis and deformity of the mandible. Anat Rec, 295:313-327, 2012 The mammalian mandible is a complex morphological structure formed by various morphogenetic components of different embryological origins. These morphogenetic components were assembled during development to form the final structure (Atchley, 1993). The mandible originates from cells of the neural crest that migrate to the first mandibular arch and form the embryonic mesenchyme, which later develops into skeletal, dental, and connective tissues. The mesenchymal cells aggregate and produce condensations before undergoing differentiation to produce the morphogenetic components of the mandible (Atchley and Hall, 1991). The mandible consists of two symmetrical halves (right and left), each formed by a dentary bone with four morphogenetic regions: the mandibular body (ramus) and three processes (coronoid, condylar, and angular).Establishing normative expectations for experimentally induced changes in size and shape will be an important innovation in three-dimensional (3-D) micro-computed tomography (CT)-based morphological assessments, especially in quantifying differences in the values of those parameters between sets of developing mandibles as a primary aim. Nondestructive methods such as micro-magnetic resonance imaging (Pieles et al., 2007) and micro-CT (Johnson et al., 2006;Boughner et al., 2008;Nagase et al., 2008;Parsons et al., 2008;Hallgrimss...

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Section: Exo Utero Surgery Of Mouse Fetuses To Restrict Temporomandibsupporting

confidence: 84%

Mathematical Analysis of Mandibular Morphogenesis by Micro‐CT‐Based Mouse and Alizarin Red S‐Stained‐Based Human Studies During Development

Rafiq

Udagawa

Lundh

et al. 2011

The Anatomical Record

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“…At E15.5, exo utero surgery was performed basically as previously described . This experimental system allows researchers to manipulate or operate live embryos of mice or rats from mid‐ to late gestation and keep them alive in situ until the effects are analyzed at a desired time point either pre‐ or postnatally .…”

Section: Methodsmentioning

confidence: 99%

In Vivo Analysis of Arg-Gly-Asp Sequence/Integrin α5β1-Mediated Signal Involvement in Embryonic Enchondral Ossification by Exo Utero Development System

Inoue

Hashimoto

Matsumoto

et al. 2013

Journal of Bone and Mineral Research

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Enchondral ossification is a fundamental mechanism for longitudinal bone growth during vertebrate development. In vitro studies suggested that functional blockade with RGD peptides or with an antibody that interferes with integrin a5b1-ligand interactions inhibited pre-hypertrophic chondrocyte differentiation. The purpose of this study is to elucidate in vivo the roles of the integrin a5b1-mediated signal through the Arg-Gly-Asp (RGD) sequence in the cell-extracellular matrix (ECM) interaction in embryonic enchondral ossification by an exo utero development system. We injected Arg-Gly-Asp-Ser (RGDS) peptides and anti-integrin a5b1 antibody (a5b1 ab) in the upper limbs of mouse embryos at embryonic day (E) 15.5 (RGDS-injected limbs, a5b1 ab-injected limbs), and compared the effects on enchondral ossification with those found in the control limbs (Arg-Gly-Glu-Ser peptide-, mouse IgG-, or vehicle-injected, and no surgery) at E16.5. In the RGDS-injected limbs, the humeri were shorter and there were fewer BrdU-positive cells than in the control limbs. The ratios of cartilage length and area to those of the humerus were higher in the RGDS-injected limbs. The ratios of type X collagen to type 2 collagen mRNA and protein (Coll X/Coll 2) were significantly lower in the RGDS-injected limbs. In those limbs, TUNEL-positive cells were hardly observed, and the ratios of fractin to the Coll X/Coll 2 ratio were lower than in the control limbs. Furthermore, the a5b1 ab-injected limbs showed results similar to those of RGDS-injected limbs. The present in vivo study by exo utero development system showed that RGDS and a5b1 ab injection decreased chondrocyte proliferation, differentiation, and apoptosis in enchondral ossification, and suggested that the integrin a5b1-mediated ECM signal through the RGD sequence is involved in embryonic enchondral ossification.

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“…Using the exo utero system (Hatta et al 2004), we have established a method to apply ACTH to mouse embryos during the histogenetic period (Zhang et al 1998(Zhang et al , 1999. Systematic examination of these ACTHtreated embryos on the tissue and organs where MC2R and/or MC5R are expressed will provide information on the role of ACTH and MCRs in mouse embryogenesis.…”

Section: Brain and Spinal Cordmentioning

confidence: 99%

“…The authors further reported that MC2R mRNA was expressed in the fetal mouse testis by RT-PCR studies, and that incubation of fetal or neonatal testis with ACTH in vitro stimulated testosterone production. We previously showed that AtT20 cells, an ACTHsecreting tumor cell line, transplanted by exo utero manipulation (Hatta et al 2004) into mouse embryos on embryonic day (E) 14.5, elevated the plasma ACTH level and changed the morphology and steroidogenesis of the adrenal cortex at E18.5 (Zhang et al 1998). These findings suggest that ACTH and its receptors (mainly MC2R and MC5R) play roles in the mouse during mouse embryogenesis.…”

Section: Introductionmentioning

confidence: 98%

Spatial and temporal patterns of expression of melanocortin type 2 and 5 receptors in the fetal mouse tissues and organs

Nimura¹,

Udagawa²,

Hatta³

et al. 2006

Anat Embryol

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In the present study to analyze the role of ACTH in fetal tissues and organs, we observed the expression of melanocortin type 2 (MC2) and 5 (MC5) receptors in ICR mouse embryos from E11.5 to E18.5 by immunohistochemistry. In the adrenal gland and testis, both receptors were expressed from E13.5 to E18.5. In the genital ridge and the ovary, melanocortin type 2 receptors (MC2R) was detected from E11.5 to E12.5 and from E13.5 to E18.5, respectively, while melanocortin type 5 receptors (MC5R) was not detected. In the mesonephros, MC2R and MC5R were expressed from E11.5 to E12.5, and in the metanephros, MC2R and MC5R were expressed from E12.5 to E18.5 and from E14.5 to E18.5, respectively. In the lung, MC2R was expressed from E11.5 to E14.5, but MC5R was not expressed at all. In blood cells, MC5R was detected at all stages examined, while MC2R was detected at none. MC2R was observed in the brain and spinal cord from E11.5 to E13.5, while MC5R was detected only in the telencephalon and only from E16.5 to E18.5. At different temporal patterns, MC2R, but not MC5R, was detected in the choroid plexus, while MC5R, but not MC2R, was expressed in the liver and in the nasal epithelium, and both MC2R and MC5R were expressed in the dorsal root ganglion and the trigeminal ganglion. These findings show the spatio-temporal specific expression patterns of MC2R and MC5R in the mouse embryo and suggest that ACTH may be related to histogenesis and/or prenatal function of various tissues and organs via MC2R and/or MC5R.

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Application of the mouse exo utero development system in the study of developmental biology and teratology

Cited by 20 publications

References 31 publications

Mathematical Analysis of Mandibular Morphogenesis by Micro‐CT‐Based Mouse and Alizarin Red S‐Stained‐Based Human Studies During Development

Mathematical Analysis of Mandibular Morphogenesis by Micro‐CT‐Based Mouse and Alizarin Red S‐Stained‐Based Human Studies During Development

In Vivo Analysis of Arg-Gly-Asp Sequence/Integrin α5β1-Mediated Signal Involvement in Embryonic Enchondral Ossification by Exo Utero Development System

Spatial and temporal patterns of expression of melanocortin type 2 and 5 receptors in the fetal mouse tissues and organs

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