Audrey Harris

UCLouvain

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Identification of regulators of V2 interneuron diversification and migration during spinal cord development

Audrey Harris

The locomotion is coordinated by neuronal circuits, named “Central Pattern Generators”, located in the ventral region of the spinal cord. These circuits are composed of motorneurons, and of dorsal or ventral interneurons (INs). Each IN population diversifies and migrates to a precise location into the spinal cord in order to properly integrate into the spinal neuronal circuits. However, the molecular mechanisms that control those processes remain poorly characterized. Recent data obtained in our laboratory have shown that the Onecut (OC) transcription factors are present in several subsets of ventral IN populations. This suggests that they could contribute to the regulation of their development. In this work, we provide evidence that the ventral IN populations diversify in multiple subpopulations regionally distributed along the antero-posterior axis of the spinal cord. We show that the OC factors are necessary for proper diversification and migration of the spinal V2 INs. Moreover, we highlight that the OC factors control the expression of Nkx6.2 and of spinal Pou2f2 isoforms. Thus, we uncover genetic cascades regulate V2 IN migration during embryonic development.%%%%(BIFA - Sciences biomedicales et pharmaceutiques) – UCL, 2018

Interneuron

Ventral nerve cord

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Eastern Visas

Geographical Journal (1939)

B. M.Audrey Harris

10.2307/1788337

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Onecut factors and Pou2f2 regulate the distribution of V2 interneurons in the mouse developing spinal cord

bioRxiv (Cold Spring Harbor Laboratory) (2018)

Audrey Harris Gauhar Masgutova Amandine Collin Mathilde Toch María Hidalgo‐Figueroa

Abstract Acquisition of proper neuronal identity and position is critical for the formation of neural circuits. In the embryonic spinal cord, cardinal populations of interneurons diversify into specialized subsets and migrate to defined locations within the spinal parenchyma. However, the factors that control interneuron diversification and migration remain poorly characterized. Here, we show that the Onecut transcription factors are necessary for proper diversification and distribution of the V2 interneurons in the developing spinal cord. Furthermore, we uncover that these proteins restrict and moderate the expression of spinal isoforms of Pou2f2 , a transcription factor known to regulate B-cell differentiation. By gain- or loss-of-function experiments, we show that Pou2f2 contribute to regulate the position of V2 populations in the developing spinal cord. Thus, we uncovered a genetic pathway that regulates the diversification and the distribution of V2 interneurons during embryonic development. Significance statement In this study, we identify the Onecut and Pou2f2 transcription factors as regulators of spinal interneuron diversification and migration, two events that are critical for proper CNS development.

Interneuron

GDF7

10.1101/413054

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Vsx1 Transiently Defines an Early Intermediate V2 Interneuron Precursor Compartment in the Mouse Developing Spinal Cord

Frontiers in Molecular Neuroscience (2016)

Cédric Francius María Hidalgo‐Figueroa Stéphanie Debrulle Barbara Pelosi Vincent Rucchin

Spinal ventral interneurons regulate the activity of motor neurons, thereby controlling motor activities. Interneurons arise during embryonic development from distinct progenitor domains distributed orderly along the dorso-ventral axis of the neural tube. A single ventral progenitor population named p2 generates at least five V2 interneuron subsets. Whether the diversification of V2 precursors into multiple subsets occurs within the p2 progenitor domain or involves a later compartment of early-born V2 interneurons remains unsolved. Here, we provide evidence that the p2 domain produces an intermediate V2 precursor compartment characterized by the transient expression of the transcriptional repressor Vsx1. These cells display an original repertoire of cellular markers distinct from that of any V2 interneuron population. They have exited the cell cycle but have not initiated neuronal differentiation. They coexpress Vsx1 and Foxn4, suggesting that they can generate the known V2 interneuron populations as well as possible additional V2 subsets. Unlike V2 interneurons, the generation of Vsx1-positive precursors does not depend on the Notch signaling pathway but expression of Vsx1 in these cells requires Pax6. Hence, the p2 progenitor domain generates an intermediate V2 precursor compartment, characterized by the presence of the transcriptional repressor Vsx1, that contributes to V2 interneuron development.

Interneuron

Compartment (ship)

Progenitor

10.3389/fnmol.2016.00145

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Citations (18)

Letters

Early Years Educator (2018)

Audrey Harris Joanne Thompson

10.12968/eyed.2018.20.6.49

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The Onecut Transcription Factors Regulate Differentiation and Distribution of Dorsal Interneurons during Spinal Cord Development

Frontiers in Molecular Neuroscience (2017)

Karolina U. Kabayiza Gauhar Masgutova Audrey Harris Vincent Rucchin Benvenuto Jacob

During embryonic development, the dorsal spinal cord generates numerous interneuron populations eventually involved in motor circuits or in sensory networks that integrate and transmit sensory inputs from the periphery. The molecular mechanisms that regulate the specification of these multiple dorsal neuronal populations have been extensively characterized. In contrast, the factors that contribute to their diversification into smaller specialized subsets and those that control the specific distribution of each population in the developing spinal cord remain unknown. Here, we demonstrate that the Onecut transcription factors, namely HNF-6 (or OC-1), OC-2 and OC-3, regulate the diversification and the distribution of spinal dorsal interneurons. Onecut proteins are dynamically and differentially distributed in dorsal interneurons during differentiation and migration. Analyzes of mutant embryos devoid of Onecut factors in the developing spinal cord evidenced a requirement in Onecut proteins for proper production of a specific subset of dI5 interneurons. In addition, the distribution of dI3, dI5 and dI6 interneuron populations was altered. Hence, Onecut transcription factors control genetic programs that contribute to the regulation of spinal dorsal interneuron diversification and distribution during embryonic development.

Interneuron

GDF7

Ventral nerve cord

10.3389/fnmol.2017.00157

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Citations (30)

Author Correction: Onecut-dependent Nkx6.2 transcription factor expression is required for proper formation and activity of spinal locomotor circuits

Scientific Reports (2020)

Mathilde Toch Audrey Harris Olivier Schakman Elena Kondratskaya Jean‐Luc Boulland

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Transcription

Expression (computer science)

10.1038/s41598-020-70339-w

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Evaluating and Choosing Journals and Editors – A Guide for Authors

Nurse author & editor (2006)

R Davidhizar Steven B. Dowd Audrey Harris

After seeing this title, you may ask: Why would an author choose where to submit work based on an editor? Shouldn't the primary consideration be the journal? One of the problems beginning authors face is finding an appropriate place for their work, and many, as editors know, choose poorly. “Have they ever even read this journal?,” many editors must wonder when they receive such things as an entire dissertation sent to a practitioner's journal or a breezy single case study report sent to a journal focusing on quantitative research. But the reality of writing for publication is that authors must choose based both on the topic presented, the editor of the journal, and the journal's editorial policy. This is something that experienced writers learn with time, and in reality it is no different whether for researchers, authors of fiction, or even composers of chess problems or crossword puzzles for game magazines. Editors are human, of course, and have all the same foibles as other people. There are certainly “bad” editors – those who don't acknowledge manuscripts in a timely fashion, those who “forget” to send papers out to reviewers, and so on. We will discuss some of these qualities in this article, but have no intention of “slamming” editors – we have served in such capacities ourselves, and have experienced many of the situations that contribute to the difficulties editors face. It is important to appreciate that editors usually have other full-time jobs. Those with academic appointments are often supposed to be granted release time for their editorial duties – an academic policy that often gets lost in the myriad responsibilities of the academic workday. One manuscript can be a day's work for the editor. They must first read the manuscript to decide whether it should go through the peer-review process, and then find the reviewers who can best evaluate the particular piece. And often editors get burned – seemingly promising reviewers do not review the manuscript properly, or let it sit on their desk until the deadline for sending it back has long passed. Experienced writers know how to choose where to send their work based on trial and error. In this article we share our personal experiences to help new authors and those hoping to establish a record of publication in their professional and academic careers. It is amazing how often journals receive totally inappropriate manuscripts. There needs to be a good fit between the topic and journal. Journals are published for readers, and not just to take up space on library shelves or, these days, in library computers. To become a good writer you must first be a critical reader of the literature. It is also imperative to read the author guidelines. Failing to do so is another common mistake. Formatting, referencing style, and the like are all important to the editor, as it is not their job to correct the manuscript for style. Such a manuscript may not even be fully read by the editor – it may be returned for not meeting the author guidelines. This error can mean that the editor will view that author with a jaded eye in the future. Experienced authors with a record of publication know where and where not to send their material. The experience of colleagues is invaluable, although not always 100% helpful. But again, it is a starting point. Sending a query with a few facts or the abstract of the article – rather than just showing the editor the manuscript – may be helpful. This can save the editor the time of reading the entire manuscript if the topic is inappropriate. A query letter or email with title, topic, research methodology, and length is helpful in soliciting interest. This can go to up to more than on editor, while a manuscript must only be submitted to one at a time. However, with journals that are published frequently and therefore deal with very large numbers of contributions, the editor may not be able to give an individualized reply and may simply advise you to go ahead and submit the article – or they may say that is appears unsuitable for their journal, of course! Mentioning a personal connection may be helpful when submitting a manuscript. That will not get it accepted, but a simple statement such as “Professor Davidhizar indicated to me that my article may be a good fit for your journal” establishes a bond and also shows that one has done one's homework! Of course, always secure permission from the person before making such statements. This can be especially helpful with journals that cover a discipline or specialty dominated by a community of well-known authors, where new authors are sometimes viewed with suspicion. Yes, the plural is intended. You should choose a primary journal for the first submission, but new authors especially should choose backups. A “backup” does not necessarily mean an inferior journal. You may find, for example, that the editor is uncommunicative, and that several months may lapse without updates. To someone on a “tenure clock” or hoping for promotion in their job, this can be particularly troublesome. Some journals are slow not because of editorial ineptitude, but because they receive a very large number of manuscripts. Also, many reviewers do this work for more than one journal and cannot always respond quickly or within the journal's target time. This means that the editor needs to find a replacement reviewer and this may result in further delay and perhaps exceeding the ideal turn-around time. All this assumes that a new author has been developmental in approach – an assumption that is perhaps incorrect. If you has never published before, it is often best to start small. One method might be to ask various journals that review new books if they need reviewers – most do. Then you can try publishing in professional magazines that are not peer reviewed, which often gives an opportunity to develop your writing skills – these magazines often have professional editors adept at cleaning up style, chopping length, and so on. If your research involves a pilot study, there are many journals that publish “shorties” – articles of perhaps 500 to 1000 words that are perfect for those interested in the topic but not in a full-blown research article. Look at copies of the magazines in your library or inspect the tables on contents on website to find this out. Never simply submit a manuscript and wait. Gentle reminders at appropriate intervals are not a problem to editors who understand the importance of people's work to their selves and careers. If an editor acts as if these gentle reminders are troublesome (e.g., “I sent you this manuscript 2 months ago and have not heard back”) or does not reply at all, it may be time to consider your backups, appropriately withdrawing the manuscript first to avoid potential duplicate publication – another professional disaster. However, withdrawing a manuscript can certainly “burn bridges” at a journal, so this should be considered carefully. Someone wanting to become a long-time contributor to the literature needs to know the appropriate outlets, which include helpful and unhelpful editors, slow and quick journals, and so on. Also, both professional editors (those who edit for a living and may or may not have content expertise) and academic editors rarely stay in the same position for long periods of time. It is not unusual to have three- to six-year cycles for academic editors, in which case previous editorial policies may remain in place or be significantly modified. Knowing the publishing cycles is important, and authors may “follow” editors as they move from one publication to another. This is not so much switching allegiance as expediting publication. Some outlets that were previously productive may dry up as editors change. Also, once you have a record of publication, you can usually withstand the wait better as the tenure and promotion clock is no longer ticking so loudly. Novice writers often become discouraged with a rejection and do nothing more with the article. Experienced writers can tell a “good” from a “bad” one. Thus, a novice learning the writing process needs to check with an experienced writer to know how to interpret editorial responses. Advice such as “What this means is that if you do these five things this journal is highly likely to print your manuscript” can spur a novice on and facilitate success. Obtaining help in understanding editorial responses can be the difference between a revision that will lead to publication and one that is a waste of time. Evaluating and choosing journals and editors wisely are every bit as important as the ability to write an elegant and articulate article. The fact is that both are essential to success in publishing your work. It is not only the ability to write that gets you published—it takes an editor accepting the article to fulfil your dream of getting it in print. Ruth Davidhizar, RN, DNS, ARNP, BC, FAAN, is Dean and Professor, Bethel College, Mishawaka, Indiana, USA. Steven B. Dowd, EdD, R.T. ®, (QM) (MR) (CT) (M) is Associate Professor, School of Health Related Professions, Medical Imaging and Therapy, University of Alabama at Birmingham, Birmingham, Alabama, USA. Audrey Harris is Assistant Professor, School of Health Related Professions, Medical Imaging and Therapy, University of Alabama at Birmingham, Birmingham, Alabama, USA.

Wonder

10.1111/j.1750-4910.2006.tb00064.x

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Citations (1)

Differential distribution of V2b interneuron subdivisions along the rostrocaudal axis of the spinal cord.

Cédric Francius Audrey Harris Vincent Rucchin Timothy J. Hendricks Floor J. Stam

Interneuron

10.1371/journal.pone.0070325.g005

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Annotated bibliography of Chamaecypans nootkatensis.

Paul E. Hennon Audrey Harris

A subject index refer ences the citation numbers so that users can find literature on a range of topics about this tree species A brief summary, the majority written by the compilers, follows most of the citations Note that the common name "yellow-cedar 1 is used throughout these summaries Many common names have been used for this tree, but "yellow-cedar" seems to be the one most frequently used within the natural range and refers to the distinctive heartwood color of the tree The accepted U S common name, "Alaska-cedar" (Little 1953), was not used because it refers to only one end of the natural range of the tree Interestingly, even the scientific name has not been universally accepted Penhallow (1896), Camus (1914), Wolf (1948), and Bartel (1993) question whether there are sufficient differences between species of Chamaecypans and Cupressus to warrant Spach's (1842) construction of the genus Chamaecypans Several authors, most notably Penhallow, would return members of Chamaecypans to Cupressus (e g , Cupressus nootkatensis D Don) but maintain these taxa in a small subgenus of formally Chamaecyparis species References on yellow-cedar were found by searching eight major databases, botany and forestry sections of libraries, and the World Wide Web Some were found in the reference or literature cited sections from these papers Others were found by merely collecting photocopies and reprints of papers as we came across them over the years Please send citations or copies of new literature or older literature that we may have overlooked to one of the authors (addresses are on the inside front cover) We intend to maintain a consistently updated version of this

Bibliography

10.2737/pnw-gtr-413

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Citations (3)