A sense of place, many times over ‐ pattern formation and evolution of repetitive morphological structures

Grall, Emmanuelle; Tschopp, Patrick

doi:10.1002/dvdy.131

“…To understand the molecular basis of morphological evolution, as driven by changes in embryonic and postembryonic development, both cell-extrinsic and -intrinsic alterations need to be considered. 28 Here, we present an integrative approach to perform comparative gene coexpression analyses at the single-cell level. We demonstrate its functionality by testing single-cell transcriptomic data from the developing mouse limb for the occurrence of cell type-specific gene co-expression modules and assess their conservation and developmental dynamics in the corresponding cell populations of the chicken.…”

Section: Discussionmentioning

confidence: 99%

“…To understand the molecular basis of morphological evolution, as driven by changes in embryonic and post‐embryonic development, both cell‐extrinsic and ‐intrinsic alterations need to be considered 28 . Here, we present an integrative approach to perform comparative gene co‐expression analyses at the single‐cell level.…”

Section: Discussionmentioning

confidence: 99%

Assessing evolutionary and developmental transcriptome dynamics in homologous cell types

Feregrino

¹

,

Tschopp

²

2021

Developmental Dynamics

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Background: During development, complex organ patterns emerge through the precise temporal and spatial specification of different cell types. On an evolutionary timescale, these patterns can change, resulting in morphological diversification. It is generally believed that homologous anatomical structures are built-largely-by homologous cell types. However, whether a common evolutionary origin of such cell types is always reflected in the conservation of their intrinsic transcriptional specification programs is less clear. Results: Here, we developed a user-friendly bioinformatics workflow to detect gene co-expression modules and test for their conservation across developmental stages and species boundaries. Using a paradigm of morphological diversification, the tetrapod limb, and single-cell RNA-sequencing data from two distantly related species, chicken and mouse, we assessed the transcriptional dynamics of homologous cell types during embryonic patterning. With mouse limb data as reference, we identified 19 gene co-expression modules with varying tissue or cell type-restricted activities. Testing for co-expression conservation revealed modules with high evolutionary turnover, while others seemed maintained-to different degrees, in module make-up, density or connectivity-over developmental and evolutionary timescales. Conclusions:We present an approach to identify evolutionary and developmental dynamics in gene co-expression modules during patterning-relevant stages of homologous cell type specification using single-cell RNA-sequencing data. K E Y W O R D Scell-intrinsic transcriptional programs, cell-extrinsic signaling environments, evolution of gene expression, EvoDevo, gene co-expression modules, limb development, WGCNA | INTRODUCTIONRecent advances in single-cell technologies now enable researchers to study the molecular dynamics of pattern formation and evolution at the level of the basic biological unit of life, the individual cell. During development, starting from a single fertilized cell, various progenitor cell populations need to proliferate, differentiate, andfor some of their progeny-undergo controlled cell elimination. These processes require tight coordination, across time and space, to result in proper pattern formation of complex organs. From a cell's perspective, this

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“…To understand the molecular basis of morphological evolution, as driven by changes in embryonic and post-embryonic development, both cell-extrinsic and – intrinsic alterations need to be considered. 32 Here, we present an integrative approach to perform comparative gene co-expression analyses at the single-cell level. We demonstrate its functionality by testing single-cell transcriptomic data from the developing mouse limb for the occurrence of cell type-specific gene co-expression modules and assess their conservation and developmental dynamics in the corresponding cell populations of the chicken.…”

Section: Discussionmentioning

confidence: 99%

Assessing evolutionary and developmental transcriptome dynamics in homologous cell types

Feregrino

¹

,

Tschopp

²

2021

Preprint

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Background: During development, complex organ patterns emerge through the precise temporal and spatial specification of different cell types. On an evolutionary timescale, these patterns can change, resulting in morphological diversification. It is generally believed that homologous anatomical structures are built - largely - by homologous cell types. However, whether a common evolutionary origin of such cell types is always reflected in the conservation of their intrinsic transcriptional specification programs is less clear. Results: Here, using a paradigm of morphological diversification, the tetrapod limb, and single-cell RNA-sequencing data from two distantly related species, chicken and mouse, we assessed the transcriptional dynamics of homologous cell types during embryonic patterning. We developed a user-friendly bioinformatics workflow to detect gene co-expression modules and test for their conservation across developmental stages and species boundaries. Using mouse limb data as reference, we identified 19 gene co-expression modules with varying tissue or cell type-restricted activities. Testing for co-expression conservation revealed modules with high evolutionary turnover, while others seemed maintained - to different degrees, in module make-up, density or connectivity - over developmental and evolutionary timescales. Conclusions: We present an approach to identify evolutionary and developmental dynamics in gene co-expression modules during patterning-relevant stages of homologous cell type specification.

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“…Since interphalangeal joint number varies widely across tetrapods -ranging from 1 in the human thumb, to over 15 in certain species of whale -it suggests that the locations of these early stripes of expression are not set individually, but rather are the result of an inherently iterative developmental mechanism that places joints at regular spatial intervals along the digit. Previous studies have proposed that a Turing-like mechanism might be responsible for the development of these patterns (12)(13)(14). In this scenario, a network of interacting and diffusing biochemical signals forms a reaction-diffusion system that selforganizes into a periodic pattern (15).…”

Section: Introductionmentioning

confidence: 99%

“…Finally, congenital defects in human digit patterning are frequently associated with mutations in members of the BMP pathway, including GDF5, BMPR1B , and Noggin ( NOG ), an extracellular BMP inhibitor known to bind GDF5 (26). Based on these observations, it has been hypothesized that regulatory interactions amongst diffusible members of the BMP pathway may play a critical role in generating the periodic phalanx-joint patterns characteristic of tetrapod digits (11, 13).…”

Section: Introductionmentioning

confidence: 99%

Self-organized BMP signaling dynamics underlie the development and evolution of tetrapod digit patterns

Grall

¹

,

Feregrino

²

,

Fischer

³

et al. 2023

Preprint

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1

0

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Repeating patterns of synovial joints are a highly conserved feature of articulated digits, with variations in joint number and location giving rise to a diverse range of digit morphologies and limb functions across the tetrapod clade. During development, joints form iteratively within the growing digit ray, as a population of distal progenitors alternately specifies joint and phalanx cell fates to segment the digit into distinct elements. Whilst numerous molecular pathways have been implicated in this fate choice, it remains unclear how they give rise to a repeating pattern. Here, using single cell RNA-sequencing and spatial gene expression profiling, we investigate the transcriptional dynamics of interphalangeal joint specification in vivo. Combined with mathematical modelling, we predict that interactions within the BMP signaling pathway - between the ligand GDF5, the inhibitor NOG, and the intracellular effector pSMAD - result in a self-organizing Turing system that forms periodic joint patterns. Our model is able to recapitulate the spatiotemporal gene expression dynamics observed in vivo, as well as phenocopy digit malformations caused by BMP pathway perturbations. By contrasting in silico simulations with in vivo morphometrics of two morphologically distinct digits, we show how changes in signaling parameters and growth dynamics can result in variations in the size and number of phalanges. Together, our results reveal a self- organizing mechanism that underpins tetrapod digit patterning and its evolvability, and, more broadly, illustrate how Turing systems based on a single molecular pathway may generate complex repetitive patterns in a wide variety of organisms.

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A sense of place, many times over ‐ pattern formation and evolution of repetitive morphological structures

Cited by 7 publications

References 153 publications

Assessing evolutionary and developmental transcriptome dynamics in homologous cell types

Assessing evolutionary and developmental transcriptome dynamics in homologous cell types

Assessing evolutionary and developmental transcriptome dynamics in homologous cell types

Self-organized BMP signaling dynamics underlie the development and evolution of tetrapod digit patterns

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