1110-0559 © 2013 The Egyptian Journal of Histology DOI: 10.1097/01.EHX.0000429789.81090.c1 1 Introduction The contact between cells and their microenvironment is fundamental both during development and for the preservation of tissue structure. Picking out signals coming from the surrounding environment enables cells to react promptly to changes that may occur. The various molecular mechanisms that explain the ability of cells to sense the microenvironment can be grouped into two major classes: (a) transmission of signals in the form of soluble molecules that interact with cellular receptors, such as growth factors, cytokines, hormones, etc.; and (b) the interaction of cells with structural components of their environment – namely other cells and the extracellular matrix (ECM) [1]. A common theme for heterotypic cell interactions is the interaction of parenchymal cells with nonparenchymal neighbors with the resultant modulation of cell growth, migration, and/or differentiation. Specifically, these interactions are of fundamental importance in physiology [2,3], pathophysiology [4], cancer [5,6] developmental biology [7], wound healing [8,9], and attempts to replace tissue function through ‘tissue engineering’ [10]. Further understanding of how cell–cell interactions modulate tissue function will allow us to gain fundamental biological insight as well as suggest approaches that will allow the manipulation of tissue function in vitro and for therapeutic applications in vivo [11]. Cell–cell interaction during the embryonic period Cell–cell interaction in the embryo was described in the literature to have a vital role in cell differentiation and development, a process generally referred to as embryonic induction [12]. Jessell and Meltont in their studies on the diffusible factors in vertebrate embryonic induction reported that one group of cells controls the fate of neighboring cells. Inductive interactions involve two primary components: a signal that is generated by the inducing cell and a receptive system that directly or indirectly controls gene expression in the responding cell [12]. The competence of cells to respond to the ligand also contributes to the extent of induction. It may be controlled by modifying the expression or function of the appropriate receptors, the intracellular signal transduction pathway, or the transcription of target genes. Inductive signals can also control the multicellular pattern if the response of similar cells to different concentrations of the same signal results in different cell fates [12]. Schmidt et al. [13] reported that signals originating from the embryonic ectoderm have a role in the development of underlying somites and the neural crest, which is mediated by the Wnt family of secreted signaling molecules that controls a wide range of developmental processes in all metazoans. Signaling molecules of the Wnt, BMP, and FGF families and their downstream effectors have been shown to mediate neural crest induction [14,15]. a Department of Anatomy, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia, b Department of Histology and Cytology, Mansoura University, Mansoura and c Department of Histology and Cytology, Assiut University, Assiut, Egypt Correspondence to Nasra N. Ayoub, Department of Anatomy, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia Tel: +966 530 112 205; fax: +966 640 0855; e-mails: nasraayuob@gmail.com, nayuob@kau.edu.sa Received ■ ■ ■■■■ Accepted ■ ■ ■■■■ The Egyptian Journal of Histology 2013, 36:000-000 00 (0000-2013) Cell–cell interactions are central to the function of many organ systems. The contact between cells and their microenvironment is fundamental both during development and for the preservation of tissue structure. Picking out the signals coming from the surrounding environment enables cells to react promptly to changes that may occur. This work provides a comprehensive review on cell interactions and cross- talk in normal physiological and some pathological conditions of different tissues and organs of the human body (e.g. embryonic, vascular, dendritic, natural killer, cardiac, nerve, lung, testicular, epidermal, and dermal cells). It aimed to explore the nature of this phenomenon and its role in regulating or directing normal cellular function. The mode of cellular interaction was discussed on the basis of biochemical data regarding cytokines or through actual cell contact through different types of junctions or synaptic ribbons. Further understanding of how cell–cell interactions modulate tissue function will allow us to gain fundamental biological insight as well as suggest approaches that will allow the manipulation of tissue function in vitro and for therapeutic applications in vivo. Keywords: cell interaction, cytokines, function, organ, structure, talk Egypt J Histol 36:000-000 © 2013 The Egyptian Journal of Histology 1110-0559 Cell cross-talk and interactions: a review of structure and function Nasra N. Ayuob a,b and Soad S. Ali a,c AQ 2 AQ 3 AQ 4 AQ 5 AQ 6 AQ 7 AQ 8 EHX362-19 Review article