Jenny Kretzschmar

MRC Laboratory of Molecular Biology

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Marko Brankatschk

TU Dresden

Caren Norden

Instituto Gulbenkian de Ciência

Elisa Nerli

Instituto Gulbenkian de Ciência

Maurício Rocha-Martins

Universidade Federal do Rio de Janeiro

Laura Christin Trautenberg

National Center for Genetic Engineering and Biotechnology

Tommaso Bianucci

TU Dresden

Ines C. Kübler

University Hospital Carl Gustav Carus

Martin Weigert

École Polytechnique Fédérale de Lausanne

Elodie Prince

Centre National de la Recherche Scientifique

Tatiana Sandoval‐Guzmán

Paul Langerhans Institute Dresden

Cooperative Institutions

TU Dresden

Max Planck Institute of Molecular Cell Biology and Genetics

Center for Systems Biology Dresden

Max Planck Society

University Hospital Carl Gustav Carus

National Center for Genetic Engineering and Biotechnology

Instituto Gulbenkian de Ciência

Paul Langerhans Institute Dresden

Max Planck Institut für Zellbiologie

MRC Laboratory of Molecular Biology

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Local problems need global solutions: The metabolic needs of regenerating organisms

Wound Repair and Regeneration (2022)

Ines C. Kübler Jenny Kretzschmar Marko Brankatschk Tatiana Sandoval‐Guzmán

The vast majority of species that belong to the plant or animal kingdom evolved with two main strategies to counter tissue damage-scar formation and regeneration. Whereas scar formation provides a fast and cost-effective repair to exit life-threatening conditions, complete tissue regeneration is time-consuming and requires vast resources to reinstall functionality of affected organs or structures. Local environments in wound healing are widely studied and findings have provided important biomedical applications. Less well understood are organismic physiological parameters and signalling circuits essential to maintain effective tissue repair. Here, we review accumulated evidence that positions the interplay of local and systemic changes in metabolism as essential variables modulating the injury response. We particularly emphasise the role of lipids and lipid-like molecules as significant components long overlooked.

Signalling pathways

Tissue Repair

10.1111/wrr.13029

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Citations (1)

Organizer activity in the mouse embryo

Cells and Development (2025)

Jenny Kretzschmar Katharine Goodwin Katie McDole

10.1016/j.cdev.2025.204001

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Diet and heat - one neuronal subset two responses

bioRxiv (Cold Spring Harbor Laboratory) (2020)

Elodie Prince Jenny Kretzschmar Laura Christin Trautenberg Marko Brankatschk

ABSTRACT The Insulin signal cascade is one of the best studied metabolic circuits, and shows a remarkable high molecular and functional conservation across the animal kingdom. Insulin-producing cells respond directly to nutritional cues in circulation and receive modulatory input from connected neuronal networks. Neuronal control is rapid and integrates a wide range of variables including dietary change or environmental temperature. However, despite various detailed studies that demonstrated the potential of neuronal regulation the physiological relevance of this circuit remains elusive. In Drosophila , Insulin-like peptide 7 (dIlp7)-producing neurons are wired with Insulin-producing cells. We found a dual role for this neuronal subset: a.) activated dilp7-producing neurons are required to facilitate development at high temperatures, and if confronted with calorie-rich food that represses neuronal activity b.) their product, dIlp7, regulates Insulin signalling levels. Our work shows that Insulin-producing cells not simply integrate signals from circulating nutritional cues and neuronal inputs, but switch to neuronal control in response to dietary composition.

Premovement neuronal activity

Biological neural network

10.1101/2020.11.18.388017

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Systemic and local lipid adaptations underlie regeneration in Drosophila melanogaster and Ambystoma mexicanum

npj Regenerative Medicine (2024)

Ines C. Kübler Jenny Kretzschmar Maria Nieves Arredondo-Lasso Sean D. Keeley Luca Claudia Rößler

Abstract In regenerating tissues, synthesis and remodeling of membranes rely on lipid turnover and transport. Our study addresses lipid adaptations in intestinal regeneration of Drosophila melanogaster and limb regeneration of Ambystoma mexicanum . We found changes in lipid profiles at different locations: transport, storage organs and regenerating tissues. We demonstrate that attenuating insulin signaling, exclusively in fat storage, inhibits the regeneration-specific response in both the fat storage and the regenerating tissue in Drosophila. Furthermore, in uninjured axolotls we found sex-specific lipid profiles in both storage and circulation, while in regenerating animals these differences subside. The regenerating limb presents a unique sterol profile, albeit with no sex differences. We postulate that regeneration triggers a systemic response, where organs storing lipids play a significant role in the regulation of systemic lipid traffic. Second, that this response may be an active and well-regulated mechanism, as observed when homeostatic sex-differences disappear in regenerating salamanders.

Ambystoma mexicanum

Homeostasis

Melanogaster

10.1038/s41536-024-00375-x

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DIlp7-Producing Neurons Regulate Insulin-Producing Cells in Drosophila

Frontiers in Physiology (2021)

Elodie Prince Jenny Kretzschmar Laura Christin Trautenberg Susanne Broschk Marko Brankatschk

Cellular Insulin signaling shows a remarkable high molecular and functional conservation. Insulin-producing cells respond directly to nutritional cues in circulation and receive modulatory input from connected neuronal networks. Neuronal control integrates a wide range of variables including dietary change or environmental temperature. Although it is shown that neuronal input is sufficient to regulate Insulin-producing cells, the physiological relevance of this network remains elusive. In Drosophila melanogaster , Insulin-like peptide7-producing neurons are wired with Insulin-producing cells. We found that the former cells regulate the latter to facilitate larval development at high temperatures, and to regulate systemic Insulin signaling in adults feeding on calorie-rich food lacking dietary yeast. Our results demonstrate a role for neuronal innervation of Insulin-producing cells important for fruit flies to survive unfavorable environmental conditions.

10.3389/fphys.2021.630390

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Citations (7)

Bidirectional neuronal migration coordinates retinal morphogenesis by preventing spatial competition

bioRxiv (Cold Spring Harbor Laboratory) (2021)

Maurício Rocha-Martins Jenny Kretzschmar Elisa Nerli Martin Weigert Jaroslav Icha

Abstract While the design of industrial products is often optimized for the sequential assembly of single components, organismal development is hallmarked by the concomitant occurrence of tissue growth and organization. Often this means that proliferating and differentiating cells occur at the same time in a shared tissue environment that continuously changes. How cells adapt to architectural changes in order to prevent spatial interference remains unclear. To understand how cell movements important for growth and organization are orchestrated, we here study the emergence of photoreceptor neurons that occur during the peak of retinal growth using zebrafish, human tissue and human organoids. Quantitative imaging reveals that successful retinal morphogenesis depends on active bidirectional photoreceptor translocation. This leads to a transient transfer of the entire cell population away from the apical proliferative zone. This migration pattern is driven by distinct cytoskeletal machineries, depending on direction: microtubules are required for basal translocation, while actomyosin drives apical movement. Blocking photoreceptor translocation leads to apical overcrowding that hampers progenitor movements. Thus, photoreceptor migration is crucial to prevent competition for space and thereby allows concurrent tissue growth and lamination. This shows that neuronal migration, in addition to its canonical role in cell positioning, is involved in coordinating morphogenesis.

10.1101/2021.02.08.430189

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Deterministic and probabilistic fate decisions co‐exist in a single retinal lineage

The EMBO Journal (2023)

Elisa Nerli Jenny Kretzschmar Tommaso Bianucci Maurício Rocha-Martins Christoph Zechner

Correct nervous system development depends on the timely differentiation of progenitor cells into neurons. While the output of progenitor differentiation is well investigated at the population and clonal level, how stereotypic or variable fate decisions are during development is still more elusive. To fill this gap, we here follow the fate outcome of single neurogenic progenitors in the zebrafish retina over time using live imaging. We find that neurogenic progenitor divisions produce two daughter cells, one of deterministic and one of probabilistic fate. Interference with the deterministic branch of the lineage affects lineage progression. In contrast, interference with fate probabilities of the probabilistic branch results in a broader range of fate possibilities than in wild-type and involves the production of any neuronal cell type even at non-canonical developmental stages. Combining the interference data with stochastic modelling of fate probabilities revealed that a simple gene regulatory network is able to predict the observed fate decision probabilities during wild-type development. These findings unveil unexpected lineage flexibility that could ensure robust development of the retina and other tissues.

Cell fate determination

Lineage (genetic)

Progenitor

Fate mapping

10.15252/embj.2022112657

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Citations (9)

Deterministic and probabilistic fate decisions co-exist in a single retinal lineage

bioRxiv (Cold Spring Harbor Laboratory) (2022)

Elisa Nerli Jenny Kretzschmar Tommaso Bianucci Maurício Rocha-Martins Christoph Zechner

Summary Correct nervous system development depends on the timely differentiation of progenitor cells into neurons. While the output of progenitor differentiation is well investigated at the population and clonal level, the possibilities and constraints for fate decisions of specific progenitors over development are less explored. Particularly little is known about their variability and competence plasticity. To fill this gap, we here use long-term live imaging to follow the outcome of progenitor divisions in the zebrafish retina. We find that neurogenic Atoh7 expressing progenitors produce different neuronal types over development with time-dependent probabilities. Interestingly, deterministic and probabilistic fate decisions co-exist in the same lineage. While interference with the deterministic fate affects lineage progression, interference with fate probabilities of the stochastic lineage branch results in a broader range of fate possibilities than seen in controls. When tissue development is challenged, Atoh7 expressing progenitors can produce any neuronal type, arguing against the concept of fixed competence windows. Stochastic modelling of fate probabilities in challenged conditions revealed a simple gene regulatory network able to recapitulate the observed competence changes during development. Based on our results, we postulate that fate plasticity could be involved in robust retinal development, a concept possibly applicable to other tissues.

Cell fate determination

Progenitor

Lineage (genetic)

10.1101/2022.08.11.503564

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Citations (7)

Neuronal migration prevents spatial competition in retinal morphogenesis

Nature (2023)

Maurício Rocha-Martins Elisa Nerli Jenny Kretzschmar Martin Weigert Jaroslav Icha

10.1038/s41586-023-06392-y

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Citations (13)