Patterning principles of morphogen gradients

Abstract

Metazoan embryos develop from a single cell into three-dimensional structured organisms while groups of genetically identical cells attain specialized identities. Cells of the developing embryo both create and accurately interpret morphogen gradients to determine their positions and make specific decisions in response. Here, we first cover intellectual roots of morphogen and positional information concepts. Focusing on animal embryos, we then provide a review of current understanding on how morphogen gradients are established and how their spans are controlled. Lastly, we cover how gradients evolve in time and space during development, and how they encode information to control patterning. In sum, we provide a list of patterning principles for morphogen gradients and review recent advances in quantitative methodologies elucidating information provided by morphogens.

Contact area and tissue growth dynamics shape synthetic juxtacrine signaling patterns

“…Such graded profiles across a tissue are well defined for morphogens, such as Decapentaplegic (Dpp) and Wingless (Wg, a Wnt homolog), that diffuse from a population of source cells and elicit growth and transcriptional responses over 30 cell diameters away 59 during normal developmental patterning 60,61 . Our observations suggest that juxtacrine signals might also have the capacity to generate similar graded profiles in development, providing the signal output is long lived and cell division sufficiently rapid.…”

“…Consistent with our model predictions, in vivo experiments show spatial exponential gradient of GFP fluorescence across the syn-Notch cell clone with several cells away from the interface exhibiting detectable synNotch output. Such graded profiles across a tissue are well defined for morphogens, such as decapentaplegic (Dpp) and Wingless (Wg, a Wnt homolog), that diffuse from a population of source cells 13 . However, regarding the question of whether an output gradient can be established in the absence of diffusible signals, we provide a plausible mechanism for spatially graded juxtacrine signal outputs.…”

“…A key challenge is to design synthetic signaling systems to create an output at precise times and locations, such that cells gain positional information and regulate cell-fate decisions 11–13 akin to how morphogen diffusion-driven concentration gradients regulate cell behaviors 14,15 . Recent studies on the spatiotemporal patterning of output in contact-mediated signaling circuits have mainly focused on in vitro implementations in fixed domains 16,17 rather than within rapidly proliferating tissues relevant during both embryo and tumor growth 18 .…”

Zebrafish as a Model to Study Retinoic Acid Signaling in Development and Disease

“…The presence of Cyp26 family enzymes is also attributed to creating “RA sinks”, which are regions of tissue that act as collecting areas for diffuse/surplus RA [ 69 , 111 , 112 , 114 , 115 ]. These “sinks” occur in part due to RAREs present in the promoters of the Cyp26a1 gene expression [ 116 , 117 , 118 , 119 , 120 ], and they contribute to the creation of RA morphogen gradients in the early embryo [ 121 , 122 , 123 , 124 , 125 , 126 , 127 ].…”

MUM, a maternal unknown message, inhibits early establishment of the medio-lateral axis in the embryo of the kelpSaccharina latissima

“…Despite the immense morphological diversity exhibited by eukaryotes, the majority of organisms can still be characterised by three primary body axes (Anlas and Trivedi, 2021). These axes can be defined based on morphological features (Barthélémy and Caraglio, 2007; Deline et al, 2018; Martinez et al, 2016), or by the presence of molecular gradients within the embryo (Friml et al, 2003; Simsek and Özbudak, 2022). Symmetry-breaking events are crucial for establishing axes within initially homogeneous states and this process is the key behind the facilitation of cell differentiation.…”