Taking too long? Close loading screen.
Connect with us

Science

Species-specific pace of development is associated with differences in protein stability

Published

on

Setting the tempo for development

Many animals display similarities in their organization (body axis, organ systems, and so on). However, they can display vastly different life spans and thus must accommodate different developmental time scales. Two studies now compare human and mouse development (see the Perspective by Iwata and Vanderhaeghen). Matsuda et al. studied the mechanism by which the human segmentation clock displays an oscillation period of 5 to 6 hours, whereas the mouse period is 2 to 3 hours. They found that biochemical reactions, including protein degradation and delays in gene expression processes, were slower in human cells compared with their mouse counterparts. Rayon et al. looked at the developmental tempo of mouse and human embryonic stem cells as they differentiate to motor neurons in vitro. Neither the sensitivity of cells to signals nor the sequence of gene-regulatory elements could explain the differing pace of differentiation. Instead, a twofold increase in protein stability and cell cycle duration in human cells compared with mouse cells was correlated with the twofold slower rate of human differentiation. These studies show that global biochemical rates play a major role in setting the pace of development.

Science, this issue p. 1450, p. eaba7667; see also p. 1431

Structured Abstract

INTRODUCTION

What determines the pace of embryonic development? Although the molecular and cellular mechanisms of many developmental processes are evolutionarily conserved, the pace at which these operate varies considerably between species. The tempo of embryonic development controls the rate of individual differentiation processes and determines the overall duration of development. Despite its importance, however, the mechanisms that control developmental tempo remain elusive.

RATIONALE

Comparing highly conserved and well-characterized developmental processes in different species permits a search for mechanisms that explain differences in tempo. The specification of neuronal subtype identity in the vertebrate spinal cord is a prominent example, lasting less than a day in zebrafish, 3 to 4 days in mouse, and around 2 weeks in human. The development of the spinal cord involves a well-defined gene regulatory program comprising a series of stereotypic changes in gene expression, regulated by extrinsic signaling as cells differentiate from neural progenitors to postmitotic neurons. The regulatory program and resulting neuronal cell types are highly similar in different vertebrates, despite the difference in tempo between species. We therefore set out to characterize the pace of differentiation of one specific neuronal subtype—motor neurons—in human and mouse and to identify molecular differences that explain differences in pace. To this end, we took advantage of the in vitro recapitulation of in vivo developmental programs using the directed differentiation of human and mouse embryonic stem cells.

RESULTS

We found that all stages of the developmental progression from neural progenitor to motor neuron were proportionally prolonged in human compared with mouse, resulting in human motor neuron differentiation taking about 2.5 times longer than mouse. Differences in tempo were not due to differences in the sensitivity of cells to signals, nor could they be attributed to differences in the sequence of the key genes or their regulatory elements. Instead, the data revealed that changes in protein stability correlated with developmental tempo, such that slower temporal progression in human corresponded to increased protein stability. An in silico model indicated that increased protein stability could account for the slower tempo of development in human compared with mouse.

CONCLUSION

The results suggest that differences in protein turnover play a role in interspecies differences in the pace of motor neuron differentiation. The identification of a molecular mechanism that can explain differences in the pace of embryonic development between species focuses attention on the role of protein stability in tempo control. This suggests a parsimonious explanation for the substantial variation in the tempo of development between species and indicates how the overall dynamics of developmental processes can be influenced by kinetic properties of gene regulation. What determines species-specific rates of protein turnover remains to be determined, but the availability of in vitro systems that mimic in vivo developmental tempo opens up the possibility of exploring this issue.

Developmental tempo and protein stability.

Different animal species develop at different tempos, and equivalent developmental stages can be matched between mouse and human at different developmental time points. Neural progenitors in the spinal cord progress through the same succession of gene expression to generate motor neurons in mouse and human, and this serves as a model to study tempo differences. The in vitro directed differentiation of mouse embryonic stem cells to motor neurons advances at greater than twice the speed of human embryonic stem cell differentiation. The equivalent progression of development at different rates is shown for the transcription factors PAX6 (green), OLIG2 (red), and NKX2.2 (blue). E, embryonic day; W, embryonic week; CS, Carnegie stage. Scale bars are 50 μm.

Abstract

Although many molecular mechanisms controlling developmental processes are evolutionarily conserved, the speed at which the embryo develops can vary substantially between species. For example, the same genetic program, comprising sequential changes in transcriptional states, governs the differentiation of motor neurons in mouse and human, but the tempo at which it operates differs between species. Using in vitro directed differentiation of embryonic stem cells to motor neurons, we show that the program runs more than twice as fast in mouse as in human. This is not due to differences in signaling, nor the genomic sequence of genes or their regulatory elements. Instead, there is an approximately two-fold increase in protein stability and cell cycle duration in human cells compared with mouse cells. This can account for the slower pace of human development and suggests that differences in protein turnover play a role in interspecies differences in developmental tempo.

Source

Continue Reading
Advertisement
Click to comment

Leave a Reply

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

Science

Too bright to breed

Published

on

Night light from coastal cities overpowers natural signals for coral spawning from neighboring reefs.

PHOTO: NOKURO/ALAMY STOCK PHOTO

Most coral species reproduce through broadcast spawning. For such a strategy to be successful, coordination has had to evolve such that gametes across clones are released simultaneously. Over millennia, lunar cycles have facilitated this coordination, but the recent development of bright artificial light has led to an overpowering of these natural signals. Ayalon et al. tested for the direct impact of different kinds of artificial light on different species of corals. The authors found that multiple lighting types, including cold and warm light-emitting diode (LED) lamps, led to loss of synchrony and spawning failure. Further, coastal maps of artificial lighting globally suggest that it threatens to interfere with coral reproduction worldwide and that the deployment of LED lights, the blue light of which penetrates deeper into the water column, is likely to make the situation even worse.

Curr. Biol. 10.1016/j.cub.2020.10.039 (2020).

Source

Continue Reading

Science

SpaceX launches Starlink app and provides pricing and service info to early beta testers

Published

on

SpaceX has debuted an official app for its Starlink satellite broadband internet service, for both iOS and Android devices. The Starlink app allows users to manage their connection – but to take part you’ll have to be part of the official beta program, and the initial public rollout of that is only just about to begin, according to emails SpaceX sent to potential beta testers this week.

The Starlink app provides guidance on how to install the Starlink receiver dish, as well as connection status (including signal quality), a device overview for seeing what’s connected to your network, and a speed test tool. It’s similar to other mobile apps for managing home wifi connections and routers. Meanwhile, the emails to potential testers that CNBC obtained detail what users can expect in terms of pricing, speeds and latency.

The initial Starlink public beta test is called the “Better than Nothing Beta Program,” SpaceX confirms in their app description, and will be rolled out across the U.S. and Canada before the end of the year – which matches up with earlier stated timelines. As per the name, SpaceX is hoping to set expectations for early customers, with speeds users can expect ranging from between 50Mb/s to 150Mb/s, and latency of 20ms to 40ms according to the customer emails, with some periods including no connectivity at all. Even with expectations set low, if those values prove accurate, it should be a big improvement for users in some hard-to-reach areas where service is currently costly, unreliable and operating at roughly dial-up equivalent speeds.

Image Credits: SpaceX

In terms of pricing, SpaceX says in the emails that the cost for participants in this beta program will be $99 per moth, plus a one-time cost of $499 initially to pay for the hardware, which includes the mounting kit and receiver dish, as well as a router with wifi networking capabilities.

The goal eventually is offer reliably, low-latency broadband that provides consistent connection by handing off connectivity between a large constellation of small satellites circling the globe in low Earth orbit. Already, SpaceX has nearly 1,000 of those launched, but it hopes to launch many thousands more before it reaches global coverage and offers general availability of its services.

SpaceX has already announced some initial commercial partnerships and pilot programs for Starlink, too, including a team-up with Microsoft to connect that company’s mobile Azure data centers, and a project with an East Texas school board to connect the local community.

Source

Continue Reading

Science

Erratum for the Report “Meta-analysis reveals declines in terrestrial but increases in freshwater insect abundances” by R. Van Klink, D. E. Bowler, K. B. Gongalsky, A. B. Swengel, A. Gentile, J. M. Chase

Published

on

S. Rennie, J. Adamson, R. Anderson, C. Andrews, J. Bater, N. Bayfield, K. Beaton, D. Beaumont, S. Benham, V. Bowmaker, C. Britt, R. Brooker, D. Brooks, J. Brunt, G. Common, R. Cooper, S. Corbett, N. Critchley, P. Dennis, J. Dick, B. Dodd, N. Dodd, N. Donovan, J. Easter, M. Flexen, A. Gardiner, D. Hamilton, P. Hargreaves, M. Hatton-Ellis, M. Howe, J. Kahl, M. Lane, S. Langan, D. Lloyd, B. McCarney, Y. McElarney, C. McKenna, S. McMillan, F. Milne, L. Milne, M. Morecroft, M. Murphy, A. Nelson, H. Nicholson, D. Pallett, D. Parry, I. Pearce, G. Pozsgai, A. Riley, R. Rose, S. Schafer, T. Scott, L. Sherrin, C. Shortall, R. Smith, P. Smith, R. Tait, C. Taylor, M. Taylor, M. Thurlow, A. Turner, K. Tyson, H. Watson, M. Whittaker, I. Woiwod, C. Wood, UK Environmental Change Network (ECN) Moth Data: 1992-2015, NERC Environmental Information Data Centre (2018); .

Source

Continue Reading

Trending