Breaking constraint of mammalian axial formulae

AbstractThe vertebral column of individual mammalian species often exhibits remarkable robustness in the number and identity of vertebral elements that form (known as axial formulae). The genetic mechanism(s) underlying this constraint however remain ill-defined. Here, we reveal the interplay of three regulatory pathways (Gdf11, miR-196 and Retinoic acid) is essential in constraining total vertebral number and regional axial identity in the mouse, from cervical through to tail vertebrae. All three pathways have differing control over Hox cluster expression, with heterochronic and quantitative changes found to parallel changes in axial identity. However, our work reveals an additional role for Hox genes in supporting axial elongation within the tail region, providing important support for an emerging view that mammalian Hox function is not limited to imparting positional identity as the mammalian body plan is laid down. More broadly, this work provides a molecular framework to interrogate mechanisms of evolutionary change and congenital anomalies of the vertebral column.

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The Usefulness of Retinoic Acid Supplementation during in Vitro Oocyte Maturation for the in Vitro Embryo Production of Livestock: A Review

Animals ◽

10.3390/ani9080561 ◽

2019 ◽

Vol 9 (8) ◽

pp. 561 ◽

Cited By ~ 4

Author(s):

Abdelnour ◽

El-Hack ◽

Swelum ◽

Saadeldin ◽

Noreldin ◽

...

Keyword(s):

Retinoic Acid ◽

Embryo Development ◽

Oocyte Maturation ◽

Mammalian Species ◽

Antioxidant Properties ◽

Reproductive Function ◽

Embryonic Growth ◽

Oxidative Damages

Retinoic acid (RA) is an indigenous metabolite and descriptive physiologically functioning constituent of vitamin A. Retinoids were documented as vital regulators for cell development and distinction, embryonic growth, and reproductive function in both male and female livestock. Previously, RA has been shown to have several positive impacts in vivo and in vitro and critically control many reproductive events, such as oocyte development, follicular growth, and early embryonic growth. In addition, RA manages apoptotic signaling and oxidative damages in cells. Recently, RA has been used widely in assisted reproductive technology fields, especially during in vitro embryo development in various mammalian species, including buffaloes, bovine, goats, sheep, pigs, and rabbits. However, the optimum concentration of RA greatly differs based on the condition of maturation media and species. Based on the obtained findings, it was generally accepted that RA enhances nuclear oocyte maturation, cleavage and maturation rates, blastocyst formation, and embryo development. As such, it possesses antioxidant properties against reactive oxygen species (ROS) and an anti-apoptotic effect through enhancing the transcription of some related genes such as superoxide dismutase, prostaglandin synthase, glutathione peroxidase, peroxiredoxins, and heme oxygenase. Therefore, the current review concludes that an addition of RA (up to 50 nM) has the potential to improve the oocyte maturation media of various species of livestock due to its antioxidant activity.

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Asymmetric robustness in the feedback control of the retinoic acid network response to environmental disturbances

10.1101/2020.07.15.203794 ◽

2020 ◽

Author(s):

Madhur Parihar ◽

Liat Bendelac-Kapon ◽

Michal Gur ◽

Abha Belorkar ◽

Sirisha Achanta ◽

...

Keyword(s):

Retinoic Acid ◽

Feedback Control ◽

Genetic Polymorphisms ◽

Pattern Analysis ◽

Environmental Changes ◽

Feedback Regulation ◽

Response Threshold ◽

Developmental Defects ◽

Regulatory Pathways ◽

Qpcr Analysis

ABSTRACTRobustness is a characteristic of regulatory pathways to ensure signal consistency in light of environmental changes or genetic polymorphisms. The retinoic acid (RA) pathway is a central developmental and tissue homeostasis regulatory signal, strongly dependent on nutritional sources of retinoids and affected by exogenous chemicals. We performed transient physiological RA signaling disturbances during embryogenesis followed by kinetic transcriptomic and high-throughput qPCR analysis of the recovery. Unbiased pattern analysis identified the RA metabolic network as the main regulated module aimed at achieving signaling robustness. We used a principal trajectory-based analysis of the clutch-dependent variability and organized the results into a robustness efficiency matrix comparing the RA feedback regulation and hox gene expression (RA targets). We found the feedback autoregulation to be sensitive to the direction of the RA perturbation: RA knockdown exhibited an upper response threshold, whereas RA addition did not activate a feedback response below a minimum threshold. These results demonstrate an asymmetric capacity for robust feedback control of the RA signal during early embryogenesis, probably based on genetic polymorphisms, likely a significant contributor to the manifestation of developmental defects.

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Influence of hematocrit on whole blood glucose levels: new evidence from marine mammals

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1989.256.6.r1220 ◽

1989 ◽

Vol 256 (6) ◽

pp. R1220-R1224 ◽

Cited By ~ 1

Author(s):

M. A. Castellini ◽

J. M. Castellini

Keyword(s):

Blood Glucose ◽

Blood Cell ◽

Red Blood Cell ◽

Glucose Concentration ◽

Whole Blood ◽

Marine Mammals ◽

Mammalian Species ◽

Regulatory Pathways ◽

Glucose Levels ◽

Blood Cell And Plasma

The water content and glucose concentration in the whole blood of marine mammals were found to be correlated to red blood cell concentration. Because hematocrit (Hct) undergoes significant periodic shifts in these mammals during periods of apnea and/or diving, the measured values of whole blood glucose change due to alterations in Hct, independent of shifts in metabolite regulatory pathways. In contrast to humans, where red blood cell and plasma glucose concentrations are equivalent, in most other mammalian species red blood cell glucose concentration is much lower than that in plasma. Therefore, as Hct increases, the whole blood concentration of glucose must decrease in a linear manner, depending on the magnitude of the Hct change and the concentration of glucose in the blood cells. This study demonstrates that water and metabolite distribution must be considered when interpreting whole blood metabolite data. The results suggest that plasma or serum analysis of metabolites would avoid distribution problems. This is especially critical in species where Hct varies during the course of the experiment, as in exercising or diving mammals.

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On peripheral control mechanisms acting on the central pattern generators for swimming in the dogfish

Journal of Experimental Biology ◽

10.1242/jeb.98.1.1 ◽

1982 ◽

Vol 98 (1) ◽

pp. 1-22 ◽

Cited By ~ 1

Author(s):

S. Grillner ◽

P. Wallen

Keyword(s):

Vertebral Column ◽

Central Pattern Generators ◽

Control Mechanisms ◽

Fictive Locomotion ◽

Tail Region ◽

Stretch Receptors ◽

Burst Pattern ◽

Ventral Roots ◽

Pattern Generators ◽

Low Amplitude

When sinusoidal movements were artificially imposed on the tail region of the curarized spinal dogfish during “fictive locomotion' the coordinated burst pattern recorded in the ventral roots was effectively entrained to follow movement frequencies above as well as below the resting rate. The entrainment was characterized by: (1) a broad range of effective movement frequencies and amplitudes (down to a few degrees); (2) frequency-dependent timing of entrained bursts to the movement; (3) constant burst durations at low and moderate frequencies; (4) incomplete entrainment in response to high or low movement frequencies combined with a low amplitude; (5) entrainment was still present when mean position of movement was displaced laterally; (6) effects persisted when the tail region was devoid of skin and muscle tissue. Entrainment effects may be explained by the activation of stretch receptors on either side of the vertebral column-spinal cord, exciting the presumed central pattern generators (CPGs) in the hemisegments ipsilateral to the stretch, while inhibiting the contralateral CPGs.

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Identification of otx2 target genes and restrictions in ectodermal competence during Xenopus cement gland formation

Development ◽

10.1242/dev.124.2.471 ◽

1997 ◽

Vol 124 (2) ◽

pp. 471-481 ◽

Cited By ~ 8

Author(s):

L.S. Gammill ◽

H. Sive

Keyword(s):

Retinoic Acid ◽

Target Genes ◽

Homeobox Gene ◽

Cement Gland ◽

Inhibitory Effects ◽

Temporal Modulation ◽

Downstream Target ◽

Positional Identity ◽

Direct Target ◽

Differentiation Marker

The homeobox gene otx2 is a key regulator of positional identity in vertebrates, however its downstream target genes and mechanism of action are not known. We have analyzed otx2 function during formation of the Xenopus cement gland, an organ that expresses otx2. The cement gland forms at early neurula from extreme anterior ectoderm and corresponds to the chin primordium of mammals. Previous studies (Blitz, I. and Cho, K. (1995) Development 121, 993–1004; Pannese, M., Polo, C., Andreazzoli, M., Vignali, R., Kablar, B., Barsacchi, G. and Boncinelli, E. (1995) Development 121, 707–720) showed that misexpressed otx2 could activate cement gland formation. However, it was not clear whether this was a direct effect of otx2 or a secondary consequence of other tissues induced by otx2. In this study we ask whether otx2 activity is spatially and temporally restricted in the ectoderm and whether cement gland-specific genes are direct targets of otx2. In order to control the timing of otx2 activity, we constructed a dexamethasone-inducible otx2 protein (otx2-GR) by fusion with the ligand-binding domain of the glucocorticoid receptor. We conclude first, that regionally restricted factors regulate otx2 activity since otx2-GR is able to activate the cement gland markers XCG and XAG only in ventrolateral ectoderm, and never in the neural plate. Second, we show that temporal responsiveness of the ectoderm to otx2-GR is limited, beginning only at mid-gastrula but continuing as late as tailbud stages. Third, we show that otx2-GR activates expression of the cement gland differentiation marker XCG in the absence of protein synthesis, identifying a direct target of otx2. otx2-GR can also activate expression of the endogenous otx2 gene, defining an autoregulatory loop. Fourth, we show that otx2-GR is sufficient to overcome the inhibitory effects of retinoic acid on cement gland formation, indicating that this effect is caused by failure to express otx2. Corroboratively, we show that otx2 autoactivation is prevented by retinoic acid. Together, these findings suggest that otx2 directly controls cement gland differentiation, and that spatial and temporal modulation of otx2 activity limits cement gland formation to the front of the embryo.

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Respecification of vertebral identities by retinoic acid

Development ◽

10.1242/dev.115.2.487 ◽

1992 ◽

Vol 115 (2) ◽

pp. 487-501 ◽

Cited By ~ 15

Author(s):

M. Kessel

Keyword(s):

Retinoic Acid ◽

Vertebral Column ◽

Hox Genes ◽

Causal Relation ◽

Morphological Changes ◽

The Body ◽

Cervical Region ◽

High Dose ◽

Mesoderm Formation ◽

Acid Administration

In higher vertebrates, the formation of the body axis proceeds in a craniocaudal direction during gastrulation. Cell biological evidence suggests that mesoderm formation and specification of axial positions occur simultaneously. Exposure of gastrulating embryos to retinoic acid induces changes in axial patterns, e.g. anterior and posterior homeotic transformations of vertebrae. These morphological changes are accompanied by changes in the nonidentical, overlapping expression domains of Hox genes. In this report the influence of retinoic acid, administered at the end of and after gastrulation, on vertebral patterns is described. Anterior transformations and truncations affecting the caudal part of the vertebral column characterize animals exposed on day 8 and 9. 4 hours after retinoic acid administration on day 8 + 5 hours, Hox-1.8, Hox-1.9, and Hox-4.5 transcripts were not detected in their usual posterior expression domains, whereas transcripts of the anterior Hox-1.5 gene remained unaffected. 4 days after RA exposure on day 8 + 5 hours, Hox-1.8 expression was shifted posteriorly by an effectively low dose of RA, which induced the formation of supernumerary ribs. Hox-1.8 expression was limited to posterior, disorganized mesenchyme, bulging out neural tube, some intestinal loops and the hindlimb in truncated embryos exposed to a high dose of RA. A causal relation between the delayed activation of posterior Hox genes and anterior transformations or agenesis of vertebrae is discussed. On day 10.5 posterior transformations begin to occur in the cervical region, while later exposures again affect more caudal structures. The distribution of the transformations along the vertebral column indicates an influence of RA on migrating sclerotome cells before they are finally fixed in the cartilagenous vertebrae. The findings show that the mesodermal segments originally specified during gastrulation can be respecified in their second migratory phase, with effects spreading for a second time in a craniocaudal direction. The transformations are discussed with regard to a molecular specification of axial levels by Hox codes, defined as combinations of expressed Hox genes.

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Dystocia due to Schistosomus reflexus in a Jersey Crossbred Cow

THE INDIAN JOURNAL OF VETERINARY SCIENCES AND BIOTECHNOLOGY ◽

10.21887/ijvsbt.v12i4.7690 ◽

2017 ◽

Vol 12 (4) ◽

Author(s):

Akshay Sharma ◽

Pravesh Kumar ◽

Amit Sharma ◽

Madhumeet Singh ◽

Neelam Bhardwaj

Keyword(s):

Congenital Anomalies ◽

Vertebral Column ◽

Domestic Animals ◽

Multiple Congenital Anomalies ◽

Abdominal Organs ◽

Crossbred Cow

Congenital anomalies, and less frequently multiple congenital anomalies, are encountered in domestic animals, which in turn may cause obstetrical problems (Noakes et al., 2002). Schistosomus reflexus is characterized by anomaly of the trunk with actual angulation of vertebral column, herniation of abdominal organs and skeleton defects leading to dystocia. Only cases that display both visceral exposure and spinal inversion are considered as true Schistosomus reflexus (Laughton et al., 2005). The condition is a type of monstrosity reported most commonly in cattle (Knight, 1996; Kalirajan and Rani, 2016; Prabaharan et al., 2016), buffalo (Kumar et al., 2012), sheep (Mukasa- Mugerwa and Bekele, 1989) and goats (Barman et al., 2010). The prevalence of Schistosomus reflexus is believed to occur in cattle from as low as 0.01% (Sloss and Johnston, 1967) to 1.3% (Knight, 1996).

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378 INVOLVEMENT OF THE SPERM TAIL IN TRIGGERING OOCYTE ACTIVATION IN PIGS

Reproduction Fertility and Development ◽

10.1071/rdv22n1ab378 ◽

2010 ◽

Vol 22 (1) ◽

pp. 346

Author(s):

M. Nakai ◽

J. Ito ◽

K. Sato ◽

J. Noguchi ◽

H. Kaneko ◽

...

Keyword(s):

Mammalian Species ◽

Sperm Head ◽

Antigenic Peptide ◽

Oocyte Activation ◽

Tail Region ◽

Sperm Tail ◽

Sperm Factor ◽

Percoll Density Gradient ◽

Strong Candidate ◽

University Of Massachusetts

In mammals, repetitive increases of the intracellular Ca2+ level, known as Ca2+ oscillations, are observed in oocytes immediately after sperm-oocyte fusion, which is a prerequisite event for oocyte activation. Previous studies indicate that phospholipase C zeta (PLCζ), a strong candidate sperm factor for triggering Ca2+ oscillations, is localized in the sperm head of several mammalian species. We have reported that the rate of pronucleus formation in oocytes injected with a sperm head is lower than that for oocytes injected with a whole spermatozoon (Nakai et al. 2009 IETS). This has given rise to a hypothesis that not only the sperm head but also the tail play a role in inducing oocyte activation in pigs. In this study, we attempted to detect the localization of PLCζ in the pig sperm tail and also its ability to activate porcine oocytes after injection. To clarify the localization of PLCζ in pig sperm, frozen-thawed ejaculated pig sperm were immunostained using an anti-PLCζ antibody that has been reported previously (Kurokawa et al. 2005). Western blotting was also carried out to examine whether PLCζ (72 kDa) was present in the sperm tail. Sperm tails were detached from the head by sonication and then collected after centrifugation in a Percoll density gradient. We also confirmed whether the sperm tail itself had the ability to trigger oocyte activation using the following 4 injection groups: (1)1 sperm head (Head), (2) 1 sperm tail (Tail), (3) 1 sperm head and 1 tail (Head + Tail), and (4) Sham. The nuclear status of the injected oocyte was evaluated at 10 h after injection. In the present study, we used 3 sperm samples that were prepared from different boars. In pig sperm, the acrosome, tail, and post-acrosomal regions were stained by the PLCζ antibody. The signals in both the post-acrosomal and tail regions disappeared after pretreatment with antigenic peptide, but that in the acrosome region was retained. Furthermore, we confirmed the presence of a band of approximately 72 kDa from the sperm tail and also confirmed its disappearance upon pretreatment with antigenic peptide. The rates of oocytes released from metaphase-II arrest in the Head, Tail, and Head+Tail groups were significantly higher than that in the Sham group (P < 0.05 by ANOVA andTukey test). However, most of the oocytes in the Tail group failed to form pronuclei and showed other meiotic stages (anaphase-II, telophase-II, or metaphase-III). In conclusion, we have shown that PLCζ is expressed in the post-acrosomal and tail region of pig sperm. It is suggested that, in the pig, the sperm tail participates in the triggering of oocyte activation. The authors thankRafaelA. Fissore (Department ofVeterinary and Animal Sciences, University of Massachusetts Amherst) for providing the antigenic peptide for PLCζ. This study was supported in part by JSPS Fellowship (71310042 to M.N.) from the Japanese Society for Promotion of Science (JSPS).

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