Palma Iannarelli

Competing waves of oligodendrocytes in the forebrain and postnatal elimination of an embryonic lineage.

The developmental origin of oligodendrocyte progenitors (OLPs) in the forebrain has been controversial. We now show, by Cre-lox fate mapping in transgenic mice, that the first OLPs originate in the medial ganglionic eminence (MGE) and anterior entopeduncular area (AEP) in the ventral forebrain. From there, they populate the entire embryonic telencephalon including the cerebral cortex before being joined by a second wave of OLPs from the lateral and/or caudal ganglionic eminences (LGE and CGE). Finally, a third wave arises within the postnatal cortex. When any one population is destroyed at source by the targeted expression of diphtheria toxin, the remaining cells take over and the mice survive and behave normally, with a normal complement of oligodendrocytes and myelin. Thus, functionally redundant populations of OLPs compete for space in the developing brain. Notably, the embryonic MGE- and AEP-derived population is eliminated during postnatal life, raising questions about the nature and purpose of the competition.

Neural crest origins of the neck and shoulder

The neck and shoulder region of vertebrates has undergone a complex evolutionary history. To identify its underlying mechanisms we map the destinations of embryonic neural crest and mesodermal stem cells using Cre-recombinase-mediated transgenesis. The single-cell resolution of this genetic labelling reveals cryptic cell boundaries traversing the seemingly homogeneous skeleton of the neck and shoulders. Within this assembly of bones and muscles we discern a precise code of connectivity that mesenchymal stem cells of both neural crest and mesodermal origin obey as they form muscle scaffolds. The neural crest anchors the head onto the anterior lining of the shoulder girdle, while a Hox-gene-controlled mesoderm links trunk muscles to the posterior neck and shoulder skeleton. The skeleton that we identify as neural crest-derived is specifically affected in human Klippel–Feil syndrome, Sprengels deformity and Arnold–Chiari I/II malformation, providing insights into their likely aetiology. We identify genes involved in the cellular modularity of the neck and shoulder skeleton and propose a new method for determining skeletal homologies that is based on muscle attachments. This has allowed us to trace the whereabouts of the cleithrum, the major shoulder bone of extinct land vertebrate ancestors, which seems to survive as the scapular spine in living mammals.

The generation of adipocytes by the neural crest

Fat cells (adipocytes) develop from adipocyte precursor cells (preadipocytes) that themselves derive from mesenchymal progenitors. Although the events controlling preadipocyte differentiation into mature adipocytes have been largely explored, the mechanisms that direct mesenchymal progenitors down the adipocyte pathway remain unknown. Similarly, although adipocytes are generally thought to derive from mesoderm, key information is lacking regarding the origin and the development of the adipose tissue during embryogenesis. The aim of this study was to gain insight into the ontogeny of fat cells, both in mouse embryonic stem (mES) cell-derived cultures and during normal development. We first used genetically engineered mES cells to produce and select ES cell-derived neuroepithelial progenitors and showed that neuroectoderm, rather than mesoderm, may be a source of adipocytes in mES cell-derived cultures. We then used primary and secondary cultures of developing quail neural crest (NC) cells to demonstrate that NC cells are able, upon stimulation with defined factors, to differentiate into adipocytes, thus providing a powerful system to study the earliest stages of adipocyte differentiation. Finally, we mapped NC derivatives in vivo using Cre-mediated recombination in transgenic mice and demonstrated that a subset of adipocytes originates from the NC during normal development.

Neural Crest Origin of Perivascular Mesenchyme in the Adult Thymus

The endodermal epithelial thymus anlage develops in tight association with neural crest (NC)-derived mesenchyme. This epithelial-NC interaction is crucial for thymus development, but it is not known how NC supports thymus development or whether NC cells or their progeny make any significant contribution to the adult thymus. By nude mouse blastocyst complementation and by cell surface phenotype, we could previously separate thymus stroma into Foxn1-dependent epithelial cells and a Foxn1-independent mesenchymal cell population. These mesenchymal cells expressed vascular endothelial growth factor-A, and contributed to thymus vascularization. These data suggested a physical or functional association with thymic blood vessels, but the origin, location in the thymus, and function of these stromal cells remained unknown. Using a transgenic mouse expressing Cre recombinase in premigratory NC (Sox10-Cre), we have now fate-mapped the majority of these adult mesenchymal cells to a NC origin. NC-derived cells represent tightly vessel-associated pericytes that are sandwiched between endothelium and epithelium along the entire thymus vasculature. The ontogenetic, phenotypic, and positional definition of this distinct perivascular mesenchymal compartment provides a cellular basis for the role of NC in thymus development and possibly maintenance, and might be useful to address properties of the endothelial-epithelial barrier in the adult thymus.

English for Biomedical Scientists

Methodological Approach to English for Biomedical Scientists.- English Grammar Usage.- Usual Mistakes Made by Scientistis Speaking and Writing in English.- Writing a Manuscript.- Writing Scientific Correspondence.- Attending a Scientific Course or Conference.- Giving Presentations for Biomedical Scientists.- Chairing a Scientific Discussion.- Curriculum Vitae, Cover Letters, and Other Professional Letters.- Getting Ready for a Job Interview in English.- The Laboratory Environment.- Laboratory Writing.- Laboratory Safety and Biohazards.- Laboratory Animal Work.- Latin and Greek Terminology.- Acronyms and Abbreviations.- Conversation Survival Guide.

Getting Ready for a Job Interview in English

Unit IX has just shown you how to write a CV and cover letter that can make your qualifications and experience look competitive for a job application. So, if you got invited for an interview: congratulations, you’ve successfully passed the first round! The job, however, is far from over. If you want to finish it and get an offer for the position that you are applying for, you will have to confirm that good initial impression from your resume in a job interview. Even more, as a non-native English-speaking applicant, you will have to confirm that good first impression in an interview held in a language that is not your own.

Curriculum Vitae, Cover Letters, and Other Professional Letters

This unit will give general guidance for biomedical scientists on how to write a CV and cover letter that stand out in English and, more importantly, for an English-speaking evaluator. General guidance on the design, sections, and lay out of CV and cover letters will be provided and explained with various examples and specific templates. Professional correspondence goes well beyond CVs and cover letters. Other professional letters that will be discussed in this unit include job acceptance and declination letters, resignation letters, and reference letters.

Writing Scientific Correspondence

This unit is made up of several examples of letters sent to editors of scientific journals. Our intention is to provide you with useful tools to communicate with journal editors and reviewers in a formal manner. It is our understanding that letters to editors have quite an important, and many times overlooked, role in the fate of scientific manuscripts.

English Grammar Usage

The first chapters are probably the least read by most readers in general and scientists in particular, and in our opinion it is precisely in the first chapters that the most important information of a book is displayed. It is in its first chapters that the foundations of a book are laid, and many readers do not optimize the reading of a manual because they skip its fundamentals.

Conversation Survival Guide

Many professionals who can hold their own fairly well in a technical conversation in English find themselves at a total loss for words in other situations. This is only to be expected. Work is a big part of life, taking up a large proportion of your waking life. Dedicated scientists and physicians often spend an even larger proportion of their time immerged in their work than their counterparts in other professions, and the chances are that most of your contact with the English language is related to your work. That is well and good, but work is not everything. When you travel outside your own country, you will need to use English in many different situations. Remember – fluency builds self-confidence and the lack of fluency breeds insecurity.