What we can learn from embryos to understand the mesenchymal-to-epithelial transition in tumor progression.

Epithelial plasticity involved the terminal and transitional stages that occur during epithelial-to-mesenchymal transition (EMT) and mesenchymal-to-epithelial transition (MET), both are essential at different stages of early embryonic development that have been co-opted by cancer cells to undergo tumor metastasis. These processes are regulated at multiple instances, whereas the post-transcriptional regulation of key genes mediated by microRNAs is gaining major attention as a common and conserved pathway. In this review, we focus on discussing the latest findings of the cellular and molecular basis of the less characterized process of MET during embryonic development, with special attention to the role of microRNAs. Although we take in consideration the necessity of being cautious when extrapolating the obtained evidence, we propose some commonalities between early embryonic development and cancer progression that can shed light into our current understanding of this complex event and might aid in the design of specific therapeutic approaches.

Histone demethylase JmjD2A regulates neural crest specification.

The neural crest is a multipotent stem cell-like population that is induced during gastrulation, but only acquires its characteristic morphology, migratory ability, and gene expression profile after neurulation. This raises the intriguing possibility that precursors are actively maintained by epigenetic influences in a stem cell-like state. Accordingly, we report that dynamic histone modifications are critical for proper temporal control of neural crest gene expression in vivo. The histone demethylase, JumonjiD2A (JmjD2A/KDM4A), is expressed in the forming neural folds. Loss of JmjD2A function causes dramatic downregulation of neural crest specifier genes analyzed by multiplex NanoString and in situ hybridization. Importantly, in vivo chromatin immunoprecipitation reveals direct stage-specific interactions of JmjD2A with regulatory regions of neural crest genes, and associated temporal modifications in methylation states of lysine residues directly affected by JmjD2A activity. Our findings show that chromatin modifications directly control neural crest genes in vertebrate embryos via modulating histone methylation.

Gonadotropin-releasing hormone neuronal development during the sensitive period of temperature sex determination in the pejerrey fish, Odontesthes bonariensis.

The development of gonadotropin-releasing hormone (GnRH) neurons was studied in relation to the sensitive period of thermolabile sex determination in the pejerrey Odontesthes bonariensis, an atherinid fish from South America. Fish were raised from hatching at three different temperatures: 17 degrees C (100% females), 24 degrees C (70% females), and 29 degrees C (100% males). Three groups of immunoreactive GnRH (ir-GnRH) neurons were identified at the terminal nerve ganglion (TNG), the midbrain tegmentum (MT), and the preoptic area (POA). Immunoreactive GnRH (ir-GnRH) neurons were identified in the TNG at hatching (day 0) and in the MT at day 3 at all the experimental temperatures. In the POA ir-GnRH neurons were identified in the nucleus preopticus periventricularis simultaneously with the first appearance of ir-GnRH fibers in the pituitary on days 11, 14, and 17 for larvae kept at 29, 24, and 17 degrees C, respectively. The number of ir-GnRH neurons in the TNG did not show any statistical difference between temperatures. The number of ir-GnRH neurons in the MT increased in number during the experiment for larvae kept at 17 and 24 degrees C but decreased between days 17 and 31 in larvae kept at 29 degrees C. The number of ir-GnRH neurons in the POA increased during development with a peak at day 28 for all temperatures studied and the magnitude of this peak showed a correlation with incubation temperature. These results reinforce the notion that the hypothalamus-pituitary-gonadal axis is active during sex determination in pejerrey suggesting a possible role of the central nervous system and GnRH in this process. It is also suggested that GnRH neurons located in the preoptic area might be the physiological transducers of temperature during the temperature sensitive period in this species.

Ontogenetic development and neuroanatomical localization of growth hormone-releasing hormone (GHRH) in the brain and pituitary gland of pejerrey fish Odontesthes bonariensis.

The presence and distribution of growth hormone-releasing hormone (GHRH) were studied by immunocytochemistry in adult and developing pejerrey fish, Odontesthes bonariensis (Atheriniformes). A few perikarya and fibers with immunoreactivity to GHRH (ir-GHRH) were identified in the olfactory bulbs at hatching. One week later, scattered ir-GHRH cell bodies were observed in the preoptic area and some fibers were detected entering the pituitary gland. Isolated ir-GHRH perikarya were revealed in the hypothalamus and in the medulla oblongata (MO) 3 weeks after hatching. Seven weeks after hatching, ir-GHRH cells were also identified in the nucleus of the lateral lemniscus and the cerebellum. Both nuclei presented strong ir-GHRH projections extending rostro-ventrally. At 11 weeks after hatching another group of ir-GHRH cells were revealed in the midbrain tegmentum. After that time the pattern of distribution of ir-GHRH structures remained unchanged. At 1 week after hatching and later, the pituitary gland consistently revealed ir-GHRH cells and fibers mainly in the proximalis pars distalis and in a minor proportion of the pars intermedia since week 1. The pineal gland showed ir-GHRH cells projecting into the pineal lumen, at week 6 after hatching and later. The pineal stalk and the subcomissural organ also presented ir-GHRH structures. Additionally, ir-GHRH material was found from week 3 to the adult stage in the following extraneural organs: gills, gut, kidney and hepatopancreas. These results represent the anatomical substrate for understanding the physiology of GHRH peptide in pejerrey, adding information on the ontogeny of neural structures expressing GHRH.