Tracing the bone and the marrow through the fruitfly

While the marrow is the nutrient source of the bone, the bone in its turn provides the environment essential for the marrow

May 27, 2015 10:48 pm | Updated 10:48 pm IST

Hematopoiesis does not stop at the pupal stage but continues in the adult fly.

Hematopoiesis does not stop at the pupal stage but continues in the adult fly.

Bones are not solid rods, they are tubes. And within their hollow is the marrow, the very seed bed of our daily life. It is from the marrow that we obtain our lifeline, our blood. Hippocrates of ancient Greece talked about marrow as a nutrient. Shakespeare in Macbeth shouts: “Avaunt! And quit my sight! Thy bone is marrowless. Thy blood is cold”. And the contemporary scientist M Tavassoli says: “for centuries, poets, healers and philosophers saw and described the close link between blood and life. Not so the marrow. Its role as the seed bed of blood lay hidden, like a seed in the soil”.

In his eminently readable review: “The origins of bone marrow as the seed bed of our blood”, Dr Barry Cooper of Texas Oncology (Proc. Baylor Univ Med. Center 2011: 24(2) 115-118), free on the web, from where I have taken the above two quotes) describes the work of Drs. F. Neumann, G. Bizzozero and W. Osler (all of 19 century in Europe), which made us understand that it is from the marrow that we get our red blood cells (erythroids), white blood cells lymphocytes (adaptive immunity) and myelocytes (innate immunity, blood clotting) and others so essential for everybody’s life, after we are born (post–embryonic). And it is the marrow cells that also have the stemness, out of which other cells as those for muscles, nerves and so on can be generated. The marrow is not just a nourisher, it is also the source for the generation of cells needed for other tissues and organs.

And interestingly, as Tavassoli noted, while the marrow is the nutrient source of the bone, the bone in its turn provides the environment essential for the marrow; each needs the other, the niche and the factory that keeps on producing cells all the time.

All this is well for animals with bones. What about the boneless invertebrates? They too need their life-fluids for metabolism, growth, immunity and waste disposal. Evolution dictates that there must be not just a proximate source of blood generation (call it hematopoiesis in technical lingo) but an ultimate origin going back in history. What are the ancestors or precursors of the marrow; of the bone; the niche and the factory?

Primordial cells were simple and single cell organisms. Uptake of nutrients and disposal of waste were simple processes across the membrane. But when they evolved into multicellular organisms with primitive body parts, transport between and across cells required some form of a body fluid. Such a fluid should not only transport stuff but also have components that can repair damaged cells and even generate new cells and new body parts. In other words, they would have to have “stemness”— a primary source from where other types of cells can be generated — the factory” mentioned above. As evolution proceeded, complexity increased but the fundamentals were set in place.

When one wants to study such a “primitive” yet “sophisticated “ organism, one goes for an easily cultivable, mutable and easy to work with invertebrate. And the development biologist’s favourite has been the fruit flies (yes the same tiny dark one that buzzes around the bananas in the fruit-seller’s cart).

Enough is known about its metabolism, genetics and cell biology, and it is easily mutable and manipulated. And it has body parts and body fluids, so that the “origin” and development of its “marrow” and “blood” can be studied with some ease. It was with this idea that Dr. Lolitika Mandal (of IISER Mohali) started her work about a decade ago. Her question was “would these niches and cell producing factories in the fruit fly, correspond to the animal bone and marrow and do these marrow-like cells posses stemness? To put it somewhat dramatically, where is the marrow and what is the blood in the fruit fly? Or, “does our blood trace its ancestry to the fly”?

Conventional wisdom until then was that such hematopoiesis in the fly was confined to the embryonic stage, and once the larval stage goes on to the pupa, this life fluid-producing organ ruptures (breaks down) and releases the cells from there for circulation. The belief was also that the adult fly has no organ for making such blood like cells any longer. In other words, it was a one-time birthday gift for the baby fly to make do with for the rest of its life.

The mother in Lolitika perhaps felt that no mother can leave her daughter in such dire straits, and began looking for organs and tissues in the adult fly where such hematopoiesis might happen. Her husband, Sudip Mandal, gallantly joined her in this parental quest.

Landmark paper And in a landmark paper that has just been published in the journal Developmental Cell (Vol 33, May 26, 2015, pp l-11), they show that hematopoiesis in the fly does not stop at the pupal stage but continues in the adult fly, and the “niche” (equivalent of the bone if you will) are some clusters on the upper side of the fly abdomen. It is here that the equivalent of blood cells is generated and contributes to immunity as well. It is these hubs in the abdomen that are the precursors of the vertebrate bone marrow, conclude the Mandals with parental pride.

dbala@lvpei.org

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