In vitro generation of neuromesodermal progenitors reveals distinct roles for wnt signalling in the specification of spinal cord and paraxial mesoderm identity

Cells of the spinal cord and somites arise from shared, dual-fated precursors, located towards the posterior of the elongating embryo. Here we show that these neuromesodermal progenitors (NMPs) can readily be generated in vitro from mouse and human pluripotent stem cells by activating Wnt and Fgf signalling, timed to emulate in vivo development. Similar to NMPs in vivo, these cells co-express the neural factor Sox2 and the mesodermal factor Brachyury and differentiate into neural and paraxial mesoderm in vitro and in vivo. The neural cells produced by NMPs have spinal cord but not anterior neural identity and can differentiate into spinal cord motor neurons. This is consistent with the shared origin of spinal cord and somites and the distinct ontogeny of the anterior and posterior nervous system. Systematic analysis of the transcriptome during differentiation identifies the molecular correlates of each of the cell identities and the routes by which they are obtained. Moreover, we take advantage of the system to provide evidence that Brachyury represses neural differentiation and that signals from mesoderm are not necessary to induce the posterior identity of spinal cord cells. This indicates that the mesoderm inducing and posteriorising functions of Wnt signalling represent two molecularly separate activities. Together the data illustrate how reverse engineering normal developmental mechanisms allows the differentiation of specific cell types in vitro and the analysis of previous difficult to access aspects of embryo development

A gene regulatory network balances neural and mesoderm specification during vertebrate trunk development

Transcriptional networks, regulated by extracellular signals, control cell fate decisions and determine the size and composition of developing tissues. One example is the network controlling bipotent neuromesodermal progenitors (NMPs) that fuel embryo elongation by generating spinal cord and trunk mesoderm tissue. Here, we use single-cell transcriptomics to identify the molecular signature of NMPs and reverse engineer the mechanism that regulates their differentiation. Together with genetic perturbations, this reveals a transcriptional network that integrates opposing retinoic acid (RA) and Wnt signals to determine the rate at which cells enter and exit the NMP state. RA, produced by newly generated mesodermal cells, provides feedback that initiates NMP generation and induces neural differentiation, thereby coordinating the production of neural and mesodermal tissue. Together, the data define a regulatory network architecture that balances the generation of different cell types from bipotential progenitors in order to facilitate orderly axis elongation

Composition of the zooplankton community,with emphasis in copepods, in Punta Morales,Golfo de Nicoya,Costa Rica

The composition of the mesozooplanktonic community was studied in the Punta Morales estuary, Gulf of Nicoya,Pacific coast of Costa Rica,during 1997.Oblique plankton hauls were performed during high and low tide using a 280 µm mesh screen net equipped with a flowmeter.The community was characterized by holoplanktonic and meroplanktonic organisms.For the holoplanktonic community,the main groups were copepods (80%)and chaetognaths (16%).The most abundant species were the copepods Acartia lilljeborgii and Paracalanus parvus.A.lilljeborgii is a typical estuarine species that maintains high populations in estuarine systems.Meroplankton was represented mainly by crustacean larvae (66%),and icthyoplankton (18%).The dominance of crustacean larvae and icthyoplankton is an evidence of the ecological importance of the Punta Morales zone.Rev.Biol.Trop.52(4):897-902.Epub 2005 Jun 24.<br>Se estudió la composición de la comunidad mezoplanctónica en Punta Morales,Golfo de Nicoya, Pacífico de Costa Rica,en 1997,arrastrando oblicuamente una red de plancton (280 µm,con flujómetro)durante marea alta y baja.La comunidad estuvo caracterizada por la presencia de organismos holo y meroplanctónicos.Los principales grupos holoplanctónicos fueron copépodos (80%)y quetognatos (16%).Las especies más abundantes fueron los copépodos Acartia lilljeborgii y Paracalanus parvus;A. lilljeborgii es una especie estuarina típica que mantiene altas poblaciones en sistemas estuarinos.El meroplancton estuvo representado principalmente por larvas de crustáceos (66%),e ictioplancton (18%).La dominancia de larvas de crustáceos e ictioplancton evidencian la importancia ecológica de la zona de Punta Morales

Composition of the zooplankton community, with emphasis in copepods, in Punta Morales, Golfo de Nicoya, Costa Rica

The composition of the mesozooplanktonic community was studied in the Punta Morales estuary, Gulf of Nicoya, Pacific coast of Costa Rica, during 1997. Oblique plankton hauls were performed during high and low tide using a 280 μm mesh screen net equipped with a flowmeter. The community was characterized by holoplanktonic and meroplanktonic organisms. For the holoplanktonic community, the main groups were copepods (80%) and chaetognaths (16%). The most abundant species were the copepods Acartia lilljeborgii and Paracalanus parvus. A. lilljeborgii is a typical estuarine species that maintains high populations in estuarine systems. Meroplankton was represented mainly by crustacean larvae (66%), and icthyoplankton (18%). The dominance of crustacean larvae and icthyoplankton is an evidence of the ecological importance of the Punta Morales zoneSe estudió la composición de la comunidad mezoplanctónica en Punta Morales, Golfo de Nicoya, Pacífico de Costa Rica, en 1997, arrastrando oblicuamente una red de plancton (280 μm, con flujómetro) durante marea alta y baja. La comunidad estuvo caracterizada por la presencia de organismos holo y meroplanctónicos. Los principales grupos holoplanctónicos fueron copépodos (80%) y quetognatos (16%). Las especies más abundantes fueron los copépodos Acartia lilljeborgii y Paracalanus parvus; A. lilljeborgii es una especie estuarina típica que mantiene altas poblaciones en sistemas estuarinos. El meroplancton estuvo representado principalmente por larvas de crustáceos (66%), e ictioplancton (18%). La dominancia de larvas de crustáceos e ictioplancton evidencian la importancia ecológica de la zona de Punta Morales

Testing the cancer stem cell hypothesis in melanoma: The clinics will tell

Whether tumorigenic cancer stem cells (CSCs) exist in melanoma has been the focus of much controversy in recent years. A number of studies have pointed to the existence of melanoma cell sub-populations that act as CSCs and can be distinguished from other tumor cells based on specific surface marker expression or specific properties such as the capacity for extensive self-renewal. Other studies failed to identify melanoma stem cells and proposed that the potential to initiate tumors is a wide spread feature in melanoma inherent to most if not all cells of the tumor mass. As with normal stem cells, the term CSC is based on an operational definition, indicating not just a tumor-initiating cell, but also a cell with the capacity to sustain long-term tumor propagation. Therefore, the experimental set-up chosen to identify putative CSCs in melanoma is crucial: Both the method of tumor cell preparation and the procedure used to assess CSC properties in vivo influence the experimental outcome and hence its interpretation. In this review, we summarize our current knowledge on CSCs and the role of stem cell properties in melanoma and discuss recent findings with respect to their clinical relevance