Active behaviour during early development shapes glucocorticoid reactivity

Luis A. Castillo-Ramírez, Soojin Ryu, Rodrigo J. De Marco

Preprint posted on 20 March 2019

Article now published in Scientific Reports at

Establishing developing zebrafish as a model system to study how early-life stress modulates stress axis function and stress responses later in life.

Selected by Kathleen Gilmour


Across a range of vertebrates, there is evidence that early-life adversity has long-term consequences for stress responses, with the hypothalamic-pituitary-adrenal (interrenal in fish; HPA/I) axis being a likely mediator of these effects.  Activation of the HPA/I or stress axis leads to increases in circulating levels of glucocorticoid hormones, which in turn trigger responses, such as the mobilization of energy reserves, that help the animal deal with the stressor.  Developmental programming of the HPA/I axis appears to be altered by exposure to stress during early life, but the mechanisms through which early-life adversity alters stress axis development and function remain unclear.  Castillo-Ramirez and colleagues propose the developing zebrafish (Danio rerio) as a model system in which to study how early-life stress modulates HPI axis function and stress responses later in life.


Key findings

Using a spinning stir bar to create a vortex current, Castillo-Ramirez and colleagues found that larval zebrafish responded actively to the stimulus by avoiding the strongest current, orienting to swim into the current (rheotaxis), and mounting a cortisol response.  The strength of these responses reflected the speed of the vortex current.  The authors then exposed 5 days-post-fertilization (dpf) larvae to a moderate vortex current for 9 h, and assessed their cortisol responses to stressors at later stages of development.  The vortex-exposed larvae exhibited an attenuated cortisol response to the vortex current at both 6 and 10 dpf, and an attenuated cortisol response to high salinity at 6 dpf.  These data show that exposure to early-life stress can induce lasting (at least for several days) changes in stress axis activity in developing zebrafish.


Why I chose this paper

The value of embryonic and larval zebrafish for mechanistic studies of stress axis development is clear (e.g. Faught and Vijayan, 2018).  Most previous work, however, has relied on experimental manipulation of cortisol levels or glucocorticoid activity (e.g. Nesan and Vijayan, 2016; Wilson et al., 2016) rather than the endogenous cortisol response to a stressor.  By choosing to focus on the effects of an endogenous cortisol response to a moderate stressor, Castillo-Ramirez and colleagues emphasize the capacity for ordinary, every-day stress to affect development of the stress axis and hence stress reactivity later in life.  They also set the scene for future studies in which the many tools that are available for work on developing zebrafish can be harnessed to elucidate the mechanisms through which early-life stress alters stress axis activity.


What next?

With a high-throughput approach for stressing developing zebrafish in hand, the authors signal their intent to apply modern molecular and visualization approaches to the question of the proximate mechanisms linking early-life stress with stress responses later in life.  There is also a need to expand on the data reported in the present study – for example, to determine how long the damping effects of early-life stress on the cortisol response last, to explore the effects of other stressors, and to evaluate whether early-life stress affects survival and reproductive output, i.e. fitness.




Faught, E. and Vijayan, M. M. (2018). The mineralocorticoid receptor is essential for stress axis regulation in zebrafish larvae. Sci. Rep. 8, 18081.

Nesan, D. and Vijayan, M. M. (2016). Maternal cortisol mediates hypothalamus-pituitary-interrenal axis development in zebrafish. Sci. Rep. 6.

Wilson, K. S., Tucker, C. S., Al-Dujaili, E. A. S., Holmes, M. D., Hadoke, P. W. F., Kenyon, C. J., and Denvir, M. A. (2016). Early-life glucocorticoids programme behaviour and metabolism in adulthood in zebrafish. J. Endocrinol. 230, 125-142.


Tags: glucocorticoid, stress axis, zebrafish

Posted on: 5 April 2019 , updated on: 11 April 2019


Read preprint (No Ratings Yet)

Have your say

Your email address will not be published. Required fields are marked *

This site uses Akismet to reduce spam. Learn how your comment data is processed.

Sign up to customise the site to your preferences and to receive alerts

Register here

Also in the developmental biology category:

‘In preprints’ from Development 2022-2023

A list of the preprints featured in Development's 'In preprints' articles between 2022-2023


List by Alex Eve, Katherine Brown

preLights peer support – preprints of interest

This is a preprint repository to organise the preprints and preLights covered through the 'preLights peer support' initiative.


List by preLights peer support

The Society for Developmental Biology 82nd Annual Meeting

This preList is made up of the preprints discussed during the Society for Developmental Biology 82nd Annual Meeting that took place in Chicago in July 2023.


List by Joyce Yu, Katherine Brown

CSHL 87th Symposium: Stem Cells

Preprints mentioned by speakers at the #CSHLsymp23


List by Alex Eve

Journal of Cell Science meeting ‘Imaging Cell Dynamics’

This preList highlights the preprints discussed at the JCS meeting 'Imaging Cell Dynamics'. The meeting was held from 14 - 17 May 2023 in Lisbon, Portugal and was organised by Erika Holzbaur, Jennifer Lippincott-Schwartz, Rob Parton and Michael Way.


List by Helen Zenner

9th International Symposium on the Biology of Vertebrate Sex Determination

This preList contains preprints discussed during the 9th International Symposium on the Biology of Vertebrate Sex Determination. This conference was held in Kona, Hawaii from April 17th to 21st 2023.


List by Martin Estermann

Alumni picks – preLights 5th Birthday

This preList contains preprints that were picked and highlighted by preLights Alumni - an initiative that was set up to mark preLights 5th birthday. More entries will follow throughout February and March 2023.


List by Sergio Menchero et al.

CellBio 2022 – An ASCB/EMBO Meeting

This preLists features preprints that were discussed and presented during the CellBio 2022 meeting in Washington, DC in December 2022.


List by Nadja Hümpfer et al.

2nd Conference of the Visegrád Group Society for Developmental Biology

Preprints from the 2nd Conference of the Visegrád Group Society for Developmental Biology (2-5 September, 2021, Szeged, Hungary)


List by Nándor Lipták


The advances in fibroblast biology preList explores the recent discoveries and preprints of the fibroblast world. Get ready to immerse yourself with this list created for fibroblasts aficionados and lovers, and beyond. Here, my goal is to include preprints of fibroblast biology, heterogeneity, fate, extracellular matrix, behavior, topography, single-cell atlases, spatial transcriptomics, and their matrix!


List by Osvaldo Contreras

EMBL Synthetic Morphogenesis: From Gene Circuits to Tissue Architecture (2021)

A list of preprints mentioned at the #EESmorphoG virtual meeting in 2021.


List by Alex Eve

EMBL Conference: From functional genomics to systems biology

Preprints presented at the virtual EMBL conference "from functional genomics and systems biology", 16-19 November 2020


List by Jesus Victorino

Single Cell Biology 2020

A list of preprints mentioned at the Wellcome Genome Campus Single Cell Biology 2020 meeting.


List by Alex Eve

Society for Developmental Biology 79th Annual Meeting

Preprints at SDB 2020


List by Irepan Salvador-Martinez, Martin Estermann

Planar Cell Polarity – PCP

This preList contains preprints about the latest findings on Planar Cell Polarity (PCP) in various model organisms at the molecular, cellular and tissue levels.


List by Ana Dorrego-Rivas

Cell Polarity

Recent research from the field of cell polarity is summarized in this list of preprints. It comprises of studies focusing on various forms of cell polarity ranging from epithelial polarity, planar cell polarity to front-to-rear polarity.


List by Yamini Ravichandran

TAGC 2020

Preprints recently presented at the virtual Allied Genetics Conference, April 22-26, 2020. #TAGC20


List by Maiko Kitaoka et al.

3D Gastruloids

A curated list of preprints related to Gastruloids (in vitro models of early development obtained by 3D aggregation of embryonic cells). Updated until July 2021.


List by Paul Gerald L. Sanchez and Stefano Vianello

ASCB EMBO Annual Meeting 2019

A collection of preprints presented at the 2019 ASCB EMBO Meeting in Washington, DC (December 7-11)


List by Madhuja Samaddar et al.

EDBC Alicante 2019

Preprints presented at the European Developmental Biology Congress (EDBC) in Alicante, October 23-26 2019.


List by Sergio Menchero et al.

EMBL Seeing is Believing – Imaging the Molecular Processes of Life

Preprints discussed at the 2019 edition of Seeing is Believing, at EMBL Heidelberg from the 9th-12th October 2019


List by Dey Lab

SDB 78th Annual Meeting 2019

A curation of the preprints presented at the SDB meeting in Boston, July 26-30 2019. The preList will be updated throughout the duration of the meeting.


List by Alex Eve

Lung Disease and Regeneration

This preprint list compiles highlights from the field of lung biology.


List by Rob Hynds

Young Embryologist Network Conference 2019

Preprints presented at the Young Embryologist Network 2019 conference, 13 May, The Francis Crick Institute, London


List by Alex Eve

Pattern formation during development

The aim of this preList is to integrate results about the mechanisms that govern patterning during development, from genes implicated in the processes to theoritical models of pattern formation in nature.


List by Alexa Sadier

BSCB/BSDB Annual Meeting 2019

Preprints presented at the BSCB/BSDB Annual Meeting 2019


List by Dey Lab

Zebrafish immunology

A compilation of cutting-edge research that uses the zebrafish as a model system to elucidate novel immunological mechanisms in health and disease.


List by Shikha Nayar