In this review, we report and analyse the molecular factors involved in cardiogenesis from the earliest stages of development, using mainly the chick embryo as a model. The first part of the review demonstrates the areas where cardiogenic cells are located from gastrula stages, analysing a brief summary of the fate map of cardiogenic cells, from the epiblast through to the primitive heart tube. The next part analyses the commitment of pre-cardiac cells in cardiogenesis before, during, and after ingression through the primitive streak. Throughout the different journeys of the pre-cardiac cells, from the origin on the epiblast level up to the constitution of the tubular heart in the mid-line, the genes involved in the different stages of the process of cardiogenesis are very numerous. These have a greater or lesser importance depending on their specificity and the order in which they appear, bearing in mind that they become more valuable as the developmental process advances and the precursor cells start acquiring the commitment of pre-cardiac cells. Next, we show some box-filled diagrams to illustrate the dynamic gene expression pattern throughout the early stages of heart development, grouping the genes by their chronological significance. Finally, we discuss the implications that this temporal genomic expression could have in the induction and specification of the different types of cells and regions of the heart.

3-Nitropropionic acid (NPA) administration to rodents produces degeneration of the striatum, accompanied by neurological disturbances that mimic Huntington’s disease (HD) motor neurological dysfunctions. It has been shown that inflammation mediates NPA-induced brain degeneration, and activated microglia secreting cytokines interleukin-1α (IL-1α) and tumor necrosis factor α (TNFα) can induce a specific type of reactive neurotoxic astrocytes, named A1, which have been detected in post-mortem brain samples of Huntington’s, Alzheimer’s, and Parkinson’s diseases. In this work we used an experimental model based on the intraperitoneal (i.p.) administration of NPA to adult Wistar rats at doses that can elicit extensive brain degeneration, and brain samples were taken before and after extensive brain damage monitored using 2,3,5-triphenyltetrazolium chloride (TTC) staining. Western blots and immunohistochemistry of brain slices show that i.p. NPA injections elicit significant increase in the expression levels of C3α subunit, a marker of generation of neurotoxic A1 astrocytes, and of cytokines IL-1α, TNFα, and C1q within the striatum, hippocampus, and cerebellum before the appearance of the HD-related neurological dysfunctions and neuronal death induced by NPA. Noteworthy, NPA administration primarily induces the generation of A1 astrocytes in the more recent phylogenetic area of the rat cerebellum. We conclude that the activation of complement C3 protein in the brain from Wistar rats is an early event in NPA-induced brain neurodegeneration.

Deep whole genome and transcriptome sequencing have highlighted the importance of an emerging class of non-coding RNA longer than 200 nucleotides (i.e., long non-coding RNAs (lncRNAs)) that are involved in multiple cellular processes such as cell differentiation, embryonic development, and tissue homeostasis. Cancer is a prime example derived from a loss of homeostasis, primarily caused by genetic alterations both in the genomic and epigenetic landscape, which results in deregulation of the gene networks. Deregulation of the expression of many lncRNAs in samples, tissues or patients has been pointed out as a molecular regulator in carcinogenesis, with them acting as oncogenes or tumor suppressor genes. Herein, we summarize the distinct molecular regulatory mechanisms described in literature in which lncRNAs modulate carcinogenesis, emphasizing epigenetic and genetic alterations in particular. Furthermore, we also reviewed the current strategies used to block lncRNA oncogenic functions and their usefulness as potential therapeutic targets in several carcinomas.

Ate maps are required to address questions about the commitment and differentiation of precardiac cells. Here, we report a detailed study of the precardiac cells located at the level of the primitive streak, employing different experiments with a variety of techniques combining double transplantations, microinjections and immunocytochemistry. Most cells of the more rostral segments of the primitive streak were found to contribute cells to the endodermal layer, adjacent to precardiac mesodermal cells of the heart forming region whose provenance was in the immediately more caudal segments of the primitive streak. We established a close spatio-temporal relationship between the two cell layers and the expression of their specific cardiac markers (cNkx-2.5, Bmp2, Cripto, Usmaar, dHand, GATA4, Pitx2, Hex, Fgf8, AMHC1 and VMHC1). We also analyzed the ability of precardiac cells to differentiate when they are transplanted to ectopic locations or are subjected to the influence of the organizer. We propose that the precardiac cells of the primitive streak form at least two groups with different significance. One, regulated by mediation of the organizer, is located preferentially in the more rostral region of the primitive streak. It consists of the prospective cells of the endoderm layer, with a hierarchic pattern of expression of different genes characterized by its capacity for induction and regulation of a second group of cells. This second group is located preferentially in the more caudal segments, and is fated to form the precardiac mesoderm, whose differentiation would be characterized by the expression of various specific genes.