How do limbs evolve

However, the cavities within their bones indicate that the marrow processes were interconnected via blood vessels, and that they communicated with the bone marrow. This suggests that red blood cells were now produced within bone.

In most current tetrapods, the columns in the metaphysis host stem cell niches that produce the precursor cells which mature into red blood cells Orkin and Zon, For this arrangement to work, the niches need to be connected to the primary blood vessels that invade the marrow cavity: this allows red blood cells to be released from the bone into the systemic circulation Calvi et al. However, Estefa et al. In fact, the earliest evidence of communication between these two structures was found in fully terrestrial tetrapods that could reproduce on land million years ago.

Crucially there was no evidence of this connection in tetrapods from million years ago, even though these creatures could already explore land Figure 1. Producing red blood cells inside the bone marrow was thought to be required for life out of water e. Instead, they suggest that bone marrow and red cell production appeared successively rather than simultaneously during evolution, even though these characteristics are intimately linked in tetrapods today.

Next, the team endeavors to discover exactly at what point the site of red blood cell production migrated to bone marrow — and why. If this event took place in the first tetrapods to explore land, then all their descendants could have inherited this trait.

If the migration happened later, when terrestrial tetrapods had already started to occupy distinct habitats, then red blood cell production in bone marrow may have evolved several times independently. Finally, pinning down when or in which taxon red blood cell production first relocated to the marrow will help to understand the environmental or biological factors that triggered this migration.

In turn, this could shed light on the subsequent biological innovations that became unlocked when red blood cells started to be produced inside bones. This article is distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use and redistribution provided that the original author and source are credited.

Article citation count generated by polling the highest count across the following sources: Crossref , PubMed Central , Scopus. The production of blood cells haematopoiesis occurs in the limb bones of most tetrapods but is absent in the fin bones of ray-finned fish. When did long bones start producing blood cells? Recent hypotheses suggested that haematopoiesis migrated into long bones prior to the water-to-land transition and protected newly-produced blood cells from harsher environmental conditions.

However, little fossil evidence to support these hypotheses has been provided so far. Observations of the humeral microarchitecture of stem-tetrapods, batrachians, and amniotes were performed using classical sectioning and three-dimensional synchrotron virtual histology. They show that Permian tetrapods seem to be among the first to exhibit a centralised marrow organisation, which allows haematopoiesis as in extant amniotes.

The findings are reported by researchers from Tokyo Institute of Technology Tokyo Tech , the Centre for Genomic Regulation CRG, Barcelona and their collaborators in the journal eLife and give new insight into how fish evolved to live on land in the form of early tetrapods.

The first four-legged, land-living creatures -- known as early tetrapods -- evolved from fish, following the transformation of fins into limbs. This fin-to-limb evolution is a crucial, yet so far unsolved, example of how morphological changes can dramatically alter life on Earth. Now, researchers at Tokyo Tech and CRG, together with scientists across Japan and Spain, have revealed how genetic alterations governing the patterning of skeletal structures in fins may have led to the evolution of limbs and the rise of early tetrapods.

The forelimbs of tetrapod evolved from the pectoral fins of the ancestral fish. These fins contain three or more basal bones connected to the pectoral shoulder girdle.

However, the most of basal bones located in the anterior side i. Pectoral fins of catsharks also contain three basal bones as seen in the ancestral fish. Thus, the team examined the fin development of catsharks, and revealed that there was a shift in the balance of anterior thumb side and posterior pinky side fields in their fin buds compared to that in mouse limb buds.

A key regulator protein controlling the balance of anterior and posterior fields of limb buds of tetrapods is Gli3. This protein is expressed in the anterior part of limb buds, and regulates the expression of a number of genes providing cells with information about their position along the anterior-posterior axis.

For example, Alx4 and Pax9 are expressed in a small area of the anterior part of the limb bud, while Hand2 is expressed in a large area of the posterior field. To determine whether shifts in the balance of anterior and posterior field occurred during fin-to-limb evolution, Onimaru, postdoctoral researcher currently at Sharpe's lab CRG , and his colleagues carefully compared the expression, function and regulation of genes involved in anterior-posterior patterning in pectoral fins of catsharks, with those of mice.

Fish and land animals both have clusters of genes called HoxA and HoxD and both are known to be essential in fin and limb development. These Hox genes are sometimes referred to as "architect genes" as they are involved in making many of the physical structures animals possess.

However, when these Hox genes from fish were placed into mouse embryos, the genes that result in the arm were switched on but not the genes responsible for the hand or the digits. This suggests that the genetic information needed to make tetrapod limbs was already present in fish before the tetrapods evolved.

Another important conclusion of the study is that fish fins are not equivalent to the tetrapod hand and digits.

Instead, the evolution of digits in land animals involved the repurposing of existing genetic infrastructure. One of the co-authors of the study, Prof Denis Duboule, also from the University of Geneva, said: "Altogether, this suggests that our digits evolved during the fin-to-limb transition by modernisation of an already existing regulatory mechanism.

Other researchers in the field say that the study contains some flaws. Jennifer Clack, from the Cambridge University Museum of Zoology, who was not involved with the study, said using the zebrafish as a model for the experiments was a bad choice.

Prof Clack added that other finned fish such as Polydon [paddlefish] "do have that mechanism, operating in a similar way to that in tetrapods, to make a complex fin skeleton". This suggests, she said, that the zebrafish at some point lost the ability to make digits. He said that the molecular analysis was of a very high quality but that the evolutionary conclusions were flawed. Tracks record oldest land-walkers.