The understanding about 150 years ago was, that cells are simple protoplasm. Since then, science is digging deeper and deeper, unearthing how complex it is to make unicellular, and in special, multicellular organisms.
With the unraveling of recent new scientific findings, things in biology have become much more complicated than currently known. In fact, I think that the information contained in the genome is a speck, it is nothing compared to the epigenetic information landscape that participates in the orchestration and making of complex multicellular organisms. It is just a tiny fraction of the global organismal epigenomic information content. Previously, I thought that the gene regulatory network just expresses genes intracellularly, and signaling pathways would do the rest. That is not so. Signaling pathways are intertwined with higher-level regulatory networks, to crosstalk with other neighboring cells, and even with cells that are distant and apart. Extrinsic factors mediate interactions between different cells. Multicellular gene expression couples single cell gene-regulation with cell-cell signaling in a tunable manner. The key to understand organismal complexity, architecture, development, and adaptation, is to unravel the intertwined mechanisms that work on a systems-level together.
The formation of tissues, organs, and organ systems, depends on precisely coordinated intercellular gene expression during tissue self-organization. Complex gene cascades drive the cells to enter a predetermined location and differentiate in a specific direction. A very large number of interacting cells need to be able to precisely coordinate their gene expression during development, homeostasis, and in response to infection. 4 Many biological processes are strikingly precise. The development of organismal form depends on the coordinated regulation of a variety of signaling molecules and location signals, which jointly regulate the development process of cell division rate, trend, and direction of cell migration, cell differentiation, and apoptosis. 5
The intracellular gene regulatory network orchestrates gene expression on a level of individual cells. The intercellular regulatory network, on top of that, operates to orchestrate how various cells operate together as a team. Together, they form the multilayer gene regulatory network. Basically, there are hierarchies above hierarchies. 2 This constitutes a higher level of organization of the tissue and, ultimately, the organism. 3
Timing and Rhythms are fundamental to biological activities. With periods ranging from seconds in glycolytic oscillations to years in reproduction, these rhythms are among the most conspicuous, noteworthy properties of living systems. Underlying biological rhythms are networks of interacting cellular oscillators. These cellular oscillators can synchronize rhythms with a certain collective period. Timing in development has to be very precise, and it raises the question of how it was implemented.
The vertebrate segmentation clock is a molecular oscillator that regulates the development timing of head-to-tail axis in segmented animals. The process of segmentation is initiated very early in the developing vertebrate embryo and involves the generation of repeated segments, or somites, along the anterior to posterior axis. it is an exquisitely organized, multistep process.
In multicellular organisms, there are both intracellular and intercellular regulatory mechanisms. GRN inferred from whole-body and tissue RNA-Seq are different from those inferred from single cell RNA-Sequences. scRNA-Seq provides transcriptomic information at the cellular level that enables inference of intracellular GRN involved in proliferation and differentiation. In contrast, bulk RNA-Seq of the entire body and tissues could contain transcriptomic information at the cell population level.
GRN indicates the intracellular interconnections of genes in a narrow sense; intercellular regulation of genes via cell–cell communication is also a key factor to understand the regulatory mechanisms underlying multicellular organisms. GRN infer intercellular regulatory relationships related to cell–cell communication via cell signaling pathways. 1
Intercellular genetic communication is an essential requirement for coordination of cell proliferation and differentiation and has an important role in many cellular processes. Gap junction channels possess large pore allowing passage of ions and small molecules between cells. MicroRNAs (miRNAs) are small regulatory RNAs that can regulate gene expression broadly. 6
2. Hyobin Kim Robustness and Evolvability of Multilayer Gene Regulatory Networks 2018