Multiple developmental defects in Engrailed-1 mutant mice: an early mid-hindbrain deletion and patterning defects in forelimbs and sternum

Development ◽  
1994 ◽  
Vol 120 (7) ◽  
pp. 2065-2075 ◽  
Author(s):  
W. Wurst ◽  
A.B. Auerbach ◽  
A.L. Joyner

During mouse development, the homeobox-containing gene En-1 is specifically expressed across the mid-hindbrain junction, the ventral ectoderm of the limb buds, and in regions of the hindbrain, spinal cord, somites and somite-derived tissues. To address the function of En-1 during embryogenesis, we have generated mice homozygous for a targeted deletion of the En-1 homeobox. En-1 mutant mice died shortly after birth and exhibited multiple developmental defects. In the brains of newborn mutants, most of the colliculi and cerebellum were missing and the third and fourth cranial nerves were absent. A deletion of midhindbrain tissue was observed as early as 9.5 days of embryonic development and the phenotype resembles that previously reported for Wnt-1 mutant mice. In addition, patterning of the forelimb paws and sternum was disrupted, and the 13th ribs were truncated. The results of these studies suggest a cell autonomous role for En-1 in generation and/or survival of mid-hindbrain precursor cells and also a non-cell autonomous role in signalling normal development of the limbs and possibly sternum.

2021 ◽  
Vol 478 (23) ◽  
pp. 4045-4070
Author(s):  
Katharina F. Sonnen ◽  
Claudia Y. Janda

In multicellular organisms, cellular behaviour is tightly regulated to allow proper embryonic development and maintenance of adult tissue. A critical component in this control is the communication between cells via signalling pathways, as errors in intercellular communication can induce developmental defects or diseases such as cancer. It has become clear over the last years that signalling is not static but varies in activity over time. Feedback mechanisms present in every signalling pathway lead to diverse dynamic phenotypes, such as transient activation, signal ramping or oscillations, occurring in a cell type- and stage-dependent manner. In cells, such dynamics can exert various functions that allow organisms to develop in a robust and reproducible way. Here, we focus on Erk, Wnt and Notch signalling pathways, which are dynamic in several tissue types and organisms, including the periodic segmentation of vertebrate embryos, and are often dysregulated in cancer. We will discuss how biochemical processes influence their dynamics and how these impact on cellular behaviour within multicellular systems.


2007 ◽  
Vol 106 (6) ◽  
pp. 472-479
Author(s):  
Joaquim L. Reis ◽  
Jorge Correia-Pinto ◽  
Mariana P. Monteiro ◽  
Grover M. Hutchins

Antioxidants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 860
Author(s):  
Wu-Sheng Sun ◽  
Hoon Jang ◽  
Mi-Ryung Park ◽  
Keon Bong Oh ◽  
Haesun Lee ◽  
...  

Oxidative stress has been suggested to negatively affect oocyte and embryo quality and developmental competence, resulting in failure to reach full term. In this study, we investigated the effect of N-acetyl-L-cysteine (NAC), a cell-permeating antioxidant, on developmental competence and the quality of oocytes and embryos upon supplementation (0.1–10 mM) in maturation and culture medium in vitro using slaughterhouse-derived oocytes and embryos. The results show that treating oocytes with 1.0 mM NAC for 8 h during in vitro maturation attenuated the intracellular reactive oxygen species (ROS) (p < 0.05) and upregulated intracellular glutathione levels (p < 0.01) in oocytes. Interestingly, we found that NAC affects early embryonic development, not only in a dose-dependent, but also in a stage-specific, manner. Significantly (p < 0.05) decreased cleavage rates (90.25% vs. 81.46%) were observed during the early stage (days 0–2), while significantly (p < 0.05) increased developmental rates (38.20% vs. 44.46%) were observed during the later stage (from day 3) of embryonic development. In particular, NAC supplementation decreased the proportion of apoptotic blastomeres significantly (p < 0.05), resulting in enhanced hatching capability and developmental rates during the in vitro culture of embryos. Taken together, our results suggest that NAC supplementation has beneficial effects on bovine oocytes and embryos through the prevention of apoptosis and the elimination of oxygen free radicals during maturation and culture in vitro.


2016 ◽  
Vol 34 (1) ◽  
pp. 1-44
Author(s):  
Jeffrey S. Adler

On May 11, 1938, two New Orleans policemen entered the Astoria Restaurant, marched to the kitchen, and approached Loyd D. T. Washington, a 41-year-old African American cook. They informed Washington that they would be taking him to the First Precinct station for questioning, although they assured the cook that he need not change his clothes and “should be right back” to the “Negro restaurant,” where he had worked for 3 years. Immediately after arriving at the station house, police officers “surrounded” Washington, showed him a photograph of a man, and announced that he had killed a white man in Yazoo City, Mississippi, 20 years earlier. When Washington insisted that he did not know the man in the photograph, that he had never been to (or even heard of) Yazoo City, and that he had been in the army at the time of the murder, the law enforcers confined him in a cell, although they had no warrant for his arrest and did not charge him with any crime. The following day, a detective brought him to the “show-up room” in the precinct house, where he continued the interrogation and, according to Washington, “tried to make me sign papers stating that I had killed a white man” in Mississippi. As every African American New Orleanian knew, the show-up (or line-up) room was the setting where detectives tortured suspects and extracted confessions. “You know you killed him, Nigger,” the detective roared. Washington, however, refused to confess, and the detective began punching him in the face, knocking out five of his teeth. After Washington crumbled to the floor, the detective repeatedly kicked him and broke one of his ribs. The beating continued for an hour, until other policemen restrained the detective, saying “give him a chance to confess and if he doesn't you may start again.” But Washington did not confess, and the violent interrogation began anew. A short time later, another police officer interrupted the detective, telling him “do not kill this man in here, after all he is wanted in Yazoo City.” Bloodied and writhing in pain, Washington asked to contact his family, but the request was ignored. Because he had not been formally charged with a crime, New Orleans law enforcers believed that Washington had no constitutional protection again self-incrimination or coercive interrogation and no right to an arraignment or bail, and they had no obligation to contact his relatives or to provide medical care for him.


2005 ◽  
Vol 25 (23) ◽  
pp. 10407-10418 ◽  
Author(s):  
Zhong-Zhou Yang ◽  
Oliver Tschopp ◽  
Nicolas Di-Poï ◽  
Elisabeth Bruder ◽  
Anne Baudry ◽  
...  

ABSTRACT Akt/protein kinase B (PKB) plays a critical role in the regulation of metabolism, transcription, cell migration, cell cycle progression, and cell survival. The existence of viable knockout mice for each of the three isoforms suggests functional redundancy. We generated mice with combined mutant alleles of Akt1 and Akt3 to study their effects on mouse development. Here we show that Akt1 − / − Akt3 +/ − mice display multiple defects in the thymus, heart, and skin and die within several days after birth, while Akt1 +/ − Akt3 − / − mice survive normally. Double knockout (Akt1 − / − Akt3 − / −) causes embryonic lethality at around embryonic days 11 and 12, with more severe developmental defects in the cardiovascular and nervous systems. Increased apoptosis was found in the developing brain of double mutant embryos. These data indicate that the Akt1 gene is more essential than Akt3 for embryonic development and survival but that both are required for embryo development. Our results indicate isoform-specific and dosage-dependent effects of Akt on animal survival and development.


Development ◽  
1992 ◽  
Vol 114 (3) ◽  
pp. 729-741 ◽  
Author(s):  
K.G. Storey ◽  
J.M. Crossley ◽  
E.M. De Robertis ◽  
W.E. Norris ◽  
C.D. Stern

Induction and regionalisation of the chick nervous system were investigated by transplanting Hensen's node into the extra-embryonic region (area opaca margin) of a host embryo. Chick/quail chimaeras were used to determine the contributions of host and donor tissue to the supernumerary axis, and three molecular markers, Engrailed, neurofilaments (antibody 3A10) and XlHbox1/Hox3.3 were used to aid the identification of particular regions of the ectopic axis. We find that the age of the node determines the regions of the nervous system that form: young nodes (stages 2–4) induced both anterior and posterior nervous system, while older nodes (stages 5–6) have reduced inducing ability and generate only posterior nervous system. By varying the age of the host embryo, we show that the competence of the epiblast to respond to neural induction declines after stage 4. We conclude that during normal development, the initial steps of neural induction take place before stage 4 and that anteroposterior regionalisation of the nervous system may be a later process, perhaps associated with the differentiating notochord. We also speculate that the mechanisms responsible for induction of head CNS differ from those that generate the spinal cord: the trunk CNS could arise by homeogenetic induction by anterior CNS or by elongation of neural primordia that are induced very early.


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