Cross-posted from The Node:
Limited time offer until 30 April 2014. Read on.
As a developmental biologist, I have found my calling in applying what I have learned about normal embryogenesis to better understanding the pathophysiology of various human congenital malformations. Often these are rare diseases, and I work closely with patient associations devoted to those conditions and learning to live with them (or with the death of the child who had been afflicted).
Among these, the congenital melanocytic nevus (CMN) is one in which I have been interested for the longest time. I organized a conference last fall in Marseille specifically devoted to the basic biology, epidemiology and medical and psychological considerations around the largest and rarest forms of CMN. I have also assisted the existing worldwide patient groups to federate, which will help us help them build a prospective registry for further research.
I didn’t do it alone, of course. Mark Beckwith from Nevus Outreach, Inc. was the most active, and the only non-physician, member of my organizing committee. We innovated by asking all the speakers to make their presentations available online, behind an inexpensive but secure paywall, and by dubbing the presentations with the sound of their actual delivery. In some settings, this is known as a slidecast. The slides advance automatically in sync with the sound.
We also placed the videos, when relevant, of the Q&A periods following the talks. The titles of the talks in the programme are at this link, and the PDF with the abstracts and titles can be downloaded directly from this one.
The idea was to make a resource that would slowly garner hits over time, as I have done with some of my teaching in the past. However, the company hosting the slidecasts has decided to eliminate the slidecast offering for good, after seven years, in the next three months. After I paid for a subscription for a full year, of course.
So: 33 presentations from the ESPCR-sponsored International Expert Meeting on Large Congenital Melanocytic Nevi and Neurocutaneous Melanocytosis in September, 2013, are currently available online. They are web-viewable “slidecasts” (author-approved slideshows with synchronized sound from the live presentations). In addition, there are 29 videos of the corresponding question and answer sessions. The slidecasts disappear at the end of April, 2014.
You can virtually “attend” this conference for only 25 euros (approximately 35 USD or 21 GBP) by navigating to this webpage. All proceeds will directly support building a prospective patient registry by the Naevus Global international federation of advocacy groups. I’m writing this to ask you to support a worthy cause and consider learning about the direct result of the developmental biology of a neural crest derivative, gone wrong in one particular molecular way (I’ll let you discover which).
After secure payment through PayPal using either a PayPal account or a credit card, we hand-distribute unique identifiers and the address of a restricted part of the Naevus Global site. There, the order of the program is reproduced, with hyperlinks to the slidecasts and videos.
Thank you for your budding interest in current research on congenital melanocytic nevi & neurocutaneous melanocytosis! I hope you find this resource beneficial and informative, and that you will support our patient registry initiative in this manner.
Sincerely yours,
Heather C. Etchevers, Ph.D.
P.S. Added on 7 February: This is a mouse blood vessel along the underside of the forebrain, with a little cuff of melanocytes – black – instead of smooth muscle, though all of both kinds of cells in theory are carrying the same mutation that is commonly found in human CMN.
We can get some pretty black brains in this manner, but that’s not what kills the mice who end up dying. They’re not a perfect model for the human condition, partly because they’re not human.
But we all have a few pigment cells normally in our meninges (and heart valves, and some other odd sites), and the mice are no exception.
I had no idea that CMNs are related to problems with the central nervous system. I guess the phenomenon is at root a function of some defect in neural crest growth or differentiation?
Possibly even before that. It has only been a couple of years that we’re now certain that kids born with CMN have “somatic” mutations in the tissue that becomes a pigmented nevus – ie. the pigment cell itself. The cell type in which the mutation happens hasn’t been formally proven, but if you take a chunk of nevus skin you’ll find the mutation, and a chunk of unaffected skin or DNA from the blood, you won’t. There’s good evidence from animal research that the mutation is in the future pigment cell.
A smaller portion of kids with CMN are epileptic, and/or have malformations of the cerebellum or the underlying hindbrain, and/or hydrocephalus, with clear neurological symptoms. These children generally but don’t always have deposits of pigment in or on the brain that can be seen on MRI in the right conditions. But about as many asymptomatic children *also* have patches of pigment on the meninges or in the brain.
The tissue that later becomes the brain also contributes cells to that population of neural crest you evoke. I played a small part 15 years ago in showing that neural crest cells coat the blood vessels of the forebrain and face in particular. Those same cells are the precursors to pigment cells. Thus, a mutation in the early forming brain could be propagated in both the later brain, causing a malformation, and in the neural crest cells from that zone, which then go on to make pigment cells.
We’re also hearing more reports, now, of children with spinal cord cysts that cause other problems, associated with trunk-level CMN. Same principle – but no one has yet biopsied these malformed areas of the central nervous system to prove it.
Can we put photos in the comments? Because I have pretty pictures from our mouse model that we’re currently characterizing, of how the pigment cells take over from the vascular smooth muscle around the brain. Maybe I’ll just tack one on to the end of the post. (Hmm. Can’t do it; I appear to be limited in media uploads to 3 Ko.) That was a pain, but there you are.
Fascinating!
I guess you can put links to photos on Flickr…
Well, hmm, I had tried to embed one. Here’s a link, but that’s much less spectacular than just seeing it [edited: see above].
Anyhow,
I’m going to have to give all y’all a refresher course, I see 🙂
Photo inserted – if I get to be the slightest bit more regular than irregular, I’ll set up another Flickr account.