Signaling in Cell Differentiation and Morphogenesis

Abstract

SUMMARYAll the information to make a complete, fully functional living organism is encoded within the genome of the fertilized oocyte. How is this genetic code translated into the vast array of cellular behaviors that unfold during the course of embryonic development, as the zygote slowly morphs into a new organism? Studies over the last 30 years or so have shown that many of these cellular processes are driven by secreted or membrane-bound signaling molecules. Elucidating how the genetic code is translated into instructions or signals during embryogenesis, how signals are generated at the correct time and place and at the appropriate level, and finally, how these instructions are interpreted and put into action, are some of the central questions of developmental biology. Our understanding of the causes of congenital malformations and disease has improved substantially with the rapid advances in our knowledge of signaling pathways and their regulation during development. In this article, I review some of the signaling pathways that play essential roles during embryonic development. These examples show some of the mechanisms used by cells to receive and interpret developmental signals. I also discuss how signaling pathways downstream from these signals are regulated and how they induce specific cellular responses that ultimately affect cell fate and morphogenesis.

lncRNADIGITand BRD3 protein form phase-separated condensates to regulate endoderm differentiation

“…Gene expression programs that determine cell identity are regulated by specific interactions between DNA, RNA, and protein, and these expression programs change during differentiation as new interactions are created and previous interactions fall apart. Signaling pathways frequently initiate differentiation (Basson, 2012), and activin or Nodal signaling provide the primary stimulus to direct human embryonic stem cells (hESCs) to differentiate into definitive endoderm (D'Amour et al, 2005;; Kubo et al, 2004). Downstream of signaling pathways, differentiation is regulated genetically and epigenetically by coding and noncoding elements of the genome (Gifford et al, 2013).…”

Pathways Involved in Formation of Mammary Organoid Architecture Have Keys to Understanding Drug Resistance and to Discovery of Druggable Targets

“…These signals emanate from reciprocal interactions between different cellular and acellular components, forming integrated feedback loops (Xu et al 2009a;Mammoto and Ingber 2010;Patwari and Lee 2010;Basson 2012). We compared gene expression profiles of nonmalignant S1, malignant T4-2 cells, and T4-2 cells reverted with six different reverting agents, including inhibitors against EGFR, b1 integrin, and MMP9, after culturing in LrECM for 10 days.…”

Transcriptional reprogramming in fused cells is triggered by plasma-membrane diminution

“…Rapidly induced changes in fundamental cellular features such as cell shape, subcellular organization and cell bioenergetics can drive adaptive regulatory mechanisms ensuring cell survival. These changes also impact whether a cell undergoes cell proliferation or acquires a specialized function (Basson, 2012;McBeath et al, 2004;Paluch and Heisenberg, 2009;Tatapudy et al, 2017). Cell fusion, an essential process during regeneration and development, is a remarkable example of how cellular morphogenesis arising from the merging of two or more cells influences cell fate determination (Ogle et al, 2005;Oren-Suissa and Podbilewicz, 2007;Zhou and Platt, 2011), but whether the cellular changes in response to cell fusion are sufficient to promote a transcriptional program which supports the new differentiated state remains unknown.…”