scholarly journals Genetic Developmental Timing Revealed by Inter-Species Transplantations in Fish

Author(s):  
Jana Franziska Fuhrmann ◽  
Lorena Buono ◽  
Juan Ramón Martinez Morales ◽  
Lázaro Centanin

AbstractThe path from a fertilised egg to an embryo involves the coordinated formation of cell types, tissues and organs. Developmental modules (Raff, 1996) comprise discrete units specified by self-sufficient genetic programs that can interact among each other during embryogenesis. Here we took advantage of the different span of embryonic development between two far related teleosts, zebrafish (Danio rerio) and medaka (Oryzias latipes), of 3 and 9 days respectively, to explore modularity principles. We report that inter-species blastula transplantations result in the ectopic formation of a retina formed by donor cells — a module. We show that the developmental time of the retina follows a genetic program: an ectopic zebrafish retina in medaka develops with zebrafish dynamics. Heterologous transplantation results in a temporal decoupling between the donor retina and host organism, illustrated by two paradigms that require retina-host interactions: lens recruitment and retino-tectal projections. Our results uncover a new experimental system to address temporal decoupling along embryonic development, and highlight the presence of largely autonomous but yet interconnected developmental modules orchestrating organogenesis.

Development ◽  
2020 ◽  
Vol 147 (22) ◽  
pp. dev192500
Author(s):  
Jana Franziska Fuhrmann ◽  
Lorena Buono ◽  
Leonie Adelmann ◽  
Juan Ramón Martinez-Morales ◽  
Lazaro Centanin

ABSTRACTThe path from a fertilised egg to an embryo involves the coordinated formation of cell types, tissues and organs. Developmental modules comprise discrete units specified by self-sufficient genetic programs that can interact with each other during embryogenesis. Here, we have taken advantage of the different span of embryonic development between two distantly related teleosts, zebrafish (Danio rerio) and medaka (Oryzias latipes) (3 and 9 days, respectively), to explore modularity principles. We report that inter-species blastula transplantations result in the ectopic formation of a retina formed by donor cells – a module. We show that the time taken for the retina to develop follows a genetic program: an ectopic zebrafish retina in medaka develops with zebrafish dynamics. Heterologous transplantation results in a temporal decoupling between the donor retina and host organism, illustrated by two paradigms that require retina-host interactions: lens recruitment and retino-tectal projections. Our results uncover a new experimental system for addressing temporal decoupling along embryonic development, and highlight the presence of largely autonomous but interconnected developmental modules that orchestrate organogenesis.


Viruses ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 999
Author(s):  
Sue E. Crawford ◽  
Sasirekha Ramani ◽  
Sarah E. Blutt ◽  
Mary K. Estes

Historically, knowledge of human host–enteric pathogen interactions has been elucidated from studies using cancer cells, animal models, clinical data, and occasionally, controlled human infection models. Although much has been learned from these studies, an understanding of the complex interactions between human viruses and the human intestinal epithelium was initially limited by the lack of nontransformed culture systems, which recapitulate the relevant heterogenous cell types that comprise the intestinal villus epithelium. New investigations using multicellular, physiologically active, organotypic cultures produced from intestinal stem cells isolated from biopsies or surgical specimens provide an exciting new avenue for understanding human specific pathogens and revealing previously unknown host–microbe interactions that affect replication and outcomes of human infections. Here, we summarize recent biologic discoveries using human intestinal organoids and human enteric viral pathogens.


2021 ◽  
pp. 105815
Author(s):  
Julian Navarrete ◽  
Peyton Wilson ◽  
Nicholas Allsing ◽  
Chandi Gordon ◽  
Rachel Margolis ◽  
...  

2018 ◽  
Vol 42 (1) ◽  
pp. 104-111 ◽  
Author(s):  
Karthiga P. ◽  
Ponnanikajamideen M. ◽  
R. Samuel Rajendran ◽  
Gurusamy Annadurai ◽  
S. Rajeshkumar

2015 ◽  
Vol 32 (1) ◽  
pp. 7-16 ◽  
Author(s):  
Yongmei Fan ◽  
Qing Feng ◽  
Kehua Lai ◽  
Weikang Huang ◽  
Chenghui Zhang ◽  
...  

2021 ◽  
Vol 9 (A) ◽  
pp. 876-881
Author(s):  
Bakhytzhan Alzhanuly ◽  
Zhussipbek Y. Mukhatayev ◽  
Dauren M. Botbayev ◽  
Yeldar Ashirbekov ◽  
Nurlybek D. Katkenov ◽  
...  

Background: The discovery and use of CRISPR/Cas9 technology have enabled researchers throughout the globe to continuously edit genomes for the benefit of science and medicine. Diabetes type I is one field of medicine where CRISPR/Cas9 has a strong potential for cell therapy development. The long-lasting paucity of healthy cells for clinical transplantation into diabetic patients has led to the search of new methods for producing β-cells from other human cell types. Embryonic stem cells are being studied worldwide as one most promising solution of this need. Aim: The aim of the study is to to check the feasibility of modulating human insulin transcription using CRISPR/Cas9-based synthetic transcription regulation factors. Results: A new approach for creating potential therapeutic donor cells with enhanced and suppressed insulin production based on one of the latest achievements of human genome editing was developed. Both synthetic transcription activator (VP64) and transcription repressor (KRAB) proteins were shown to function adequately well as a part of the whole CRISPR/Cas9-based system. We claim that our results have a lot to offer and can bring light to many studies where numerous labs are struggling on to treat this disease.


2020 ◽  
Author(s):  
Mayukh Choudhury ◽  
Clara A. Amegandjin ◽  
Vidya Jadhav ◽  
Josianne Nunes Carriço ◽  
Ariane Quintal ◽  
...  

ABSTRACTMutations in regulators of the Mechanistic Target Of Rapamycin Complex 1 (mTORC1), such as Tsc1/2, lead to neurodevelopmental disorders associated with autism, intellectual disabilities and epilepsy. Whereas the effects of mTORC1 signaling dysfunction within diverse cell types are likely critical for the onset of the diverse neurological symptoms associated with mutations in mTORC1 regulators, they are not well understood. In particular, the effects of mTORC1 dys-regulation in specific types of inhibitory interneurons are unclear.Here, we showed that Tsc1 haploinsufficiency in parvalbumin (PV)-positive GABAergic interneurons either in cortical organotypic cultures or in vivo caused a premature increase in their perisomatic innervations, followed by a striking loss in adult mice. This effects were accompanied by alterations of AMPK-dependent autophagy in pre-adolescent but not adult mice. PV cell-restricted Tsc1 mutant mice showed deficits in social behavior. Treatment with the mTOR inhibitor Rapamycin restricted to the third postnatal week was sufficient to permanently rescue deficits in both PV cell innervation and social behavior in adult conditional haploinsufficient mice. All together, these findings identify a novel role of Tsc1-mTORC1 signaling in the regulation of the developmental time course and maintenance of cortical PV cell connectivity and provide a mechanistic basis for the targeted rescue of autism-related behaviors in disorders associated with deregulated mTORC1 signaling.


2019 ◽  
Author(s):  
Bushra Raj ◽  
Jeffrey A. Farrell ◽  
Aaron McKenna ◽  
Jessica L. Leslie ◽  
Alexander F. Schier

ABSTRACTNeurogenesis in the vertebrate brain comprises many steps ranging from the proliferation of progenitors to the differentiation and maturation of neurons. Although these processes are highly regulated, the landscape of transcriptional changes and progenitor identities underlying brain development are poorly characterized. Here, we describe the first developmental single-cell RNA-seq catalog of more than 200,000 zebrafish brain cells encompassing 12 stages from 12 hours post-fertilization to 15 days post-fertilization. We characterize known and novel gene markers for more than 800 clusters across these timepoints. Our results capture the temporal dynamics of multiple neurogenic waves from embryo to larva that expand neuronal diversity from ∼20 cell types at 12 hpf to ∼100 cell types at 15 dpf. We find that most embryonic neural progenitor states are transient and transcriptionally distinct from long-lasting neural progenitors of post-embryonic stages. Furthermore, we reconstruct cell specification trajectories for the retina and hypothalamus, and identify gene expression cascades and novel markers. Our analysis reveal that late-stage retinal neural progenitors transcriptionally overlap cell states observed in the embryo, while hypothalamic neural progenitors become progressively distinct with developmental time. These data provide the first comprehensive single-cell transcriptomic time course for vertebrate brain development and suggest distinct neurogenic regulatory paradigms between different stages and tissues.


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