Communication codes in developmental signaling pathways

Li, Pulin; Elowitz, Michael B.

doi:10.1242/dev.170977

Cited by 81 publications

(81 citation statements)

References 137 publications

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“…In combination with microfluidic or optogenetic approaches controlling morphogen signaling, such ex vivo/in vitro methods are likely to contribute to a more quantitative understanding of the underlying molecular and cellular processes . Furthermore, emerging techniques to measure and perturb various intrinsic parameters with cellular resolution will help to disentangle how virtually homogenous, extracellular positional information can be interpreted differentially cell‐intrinsically, to result in discretized cellular states . Quantitative data from these newly available technologies should in turn result in the continuing refinement of mathematical and computational models, to approximate periodic pattering of repetitive morphological structures in silico …”

Section: Discussionmentioning

confidence: 99%

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

Grall

Tschopp

2019

Developmental Dynamics

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Fifty years ago, Lewis Wolpert introduced the concept of “positional information” to explain how patterns form in a multicellular embryonic field. Using morphogen gradients, whose continuous distributions of positional values are discretized via thresholds into distinct cellular states, he provided, at the theoretical level, an elegant solution to the “French Flag problem.” In the intervening years, many experimental studies have lent support to Wolpert's ideas. However, the embryonic patterning of highly repetitive morphological structures, as often occurring in nature, can reveal limitations in the strict implementation of his initial theory, given the number of distinct threshold values that would have to be specified. Here, we review how positional information is complemented to circumvent these inadequacies, to accommodate tissue growth and pattern periodicity. In particular, we focus on functional anatomical assemblies composed of such structures, like the vertebrate spine or tetrapod digits, where the resulting segmented architecture is intrinsically linked to periodic pattern formation and unidirectional growth. These systems integrate positional information and growth with additional patterning cues that, we suggest, increase robustness and evolvability. We discuss different experimental and theoretical models to study such patterning systems, and how the underlying processes are modulated over evolutionary timescales to enable morphological diversification.

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Section: Discussionmentioning

confidence: 99%

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

Grall

Tschopp

2019

Developmental Dynamics

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“…Following Wolpert, Gierer and Meinhardt proposed models of morphogen distribution to demonstrate that relatively simple molecular mechanisms can explain the formation of a spatially patterned tissue . Subsequent experimental work has demonstrated that a core set of morphogens generate and relay positional information to cells to directly induce cellular responses based on the cells' location (reviewed in References 10 and 11).…”

Section: Introductionmentioning

confidence: 99%

Interplay between morphogen‐directed positional information systems and physiological signaling

Huizar

Soundarrajan

Paravitorghabeh

et al. 2019

Developmental Dynamics

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The development of an organism from an undifferentiated single cell into a spatially complex structure requires spatial patterning of cell fates across tissues. Positional information, proposed by Lewis Wolpert in 1969, has led to the characterization of many components involved in regulating morphogen signaling activity. However, how morphogen gradients are established, maintained, and interpreted by cells still is not fully understood. Quantitative and systems‐based approaches are increasingly needed to define general biological design rules that govern positional information systems in developing organisms. This short review highlights a selective set of studies that have investigated the roles of physiological signaling in modulating and mediating morphogen‐based pattern formation. Similarities between neural transmission and morphogen‐based pattern formation mechanisms suggest underlying shared principles of active cell‐based communication. Within larger tissues, neural networks provide directed information, via physiological signaling, that supplements positional information through diffusion. Further, mounting evidence demonstrates that physiological signaling plays a role in ensuring robustness of morphogen‐based signaling. We conclude by highlighting several outstanding questions regarding the role of physiological signaling in morphogen‐based pattern formation. Elucidating how physiological signaling impacts positional information is critical for understanding the close coupling of developmental and cellular processes in the context of development, disease, and regeneration.

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“…Upon ligand binding, FGFRs dimerize which leads to transactivation of the kinase domain, subsequent phosphorylation of intracellular tyrosines, and binding of signaling effectors that in turn orchestrate activation of downstream signaling pathways (Brewer et al, 2016;Lemmon and Schlessinger, 2010). Different thresholds in dimer strength and stability also may come into play, as well as signaling dynamics engaged by each downstream signaling pathway (Li and Elowitz, 2019;Vasudevan et al, 2015;Zinkle and Mohammadi, 2018). The signaling pathways that operate downstream of FGFR1 have been particularly well studied (reviewed in (Brewer et al, 2016)).…”

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confidence: 99%

FGF signaling in development beyond canonical pathways

Ray

Mazot

Catela

et al. 2020

Preprint

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FGFs are key developmental regulators which engage a signal transduction cascade through receptor tyrosine kinases, typically involving ERK1/2, PI3K/AKT, and other effectors. However, it remains unknown if all FGF activities depend on kinase activity or these canonical signal transduction cascades. To address these questions, we generated allelic series of knock-in Fgfr1 and Fgfr2 mouse strains, carrying point mutations that disrupt binding of signaling effectors to the receptors, alone or in combination. We also produced a kinase dead allele of Fgfr2 which broadly phenocopies the null mutant. When interrogated in cranial neural crest cells, point mutations in either receptor revealed discrete functions for signaling pathways in specific craniofacial contexts, but failed to recapitulate the single or double null mutant phenotypes even in their most extensive combination. Furthermore, we found that together these signaling mutations abrogated the established FGF-induced signal transduction pathways, yet certain FGF functions such as cell-matrix and cell-cell adhesion remained unaffected. Our studies establish combinatorial roles of both Fgfr1 and Fgfr2 in development and identify novel kinase-dependent cell adhesion properties of FGF receptors, independent of well-established roles in intracellular signaling.

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Communication codes in developmental signaling pathways

Cited by 81 publications

References 137 publications

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

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

Interplay between morphogen‐directed positional information systems and physiological signaling

FGF signaling in development beyond canonical pathways

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