Tetrapod | EPFL Graph Search

Tetrapods ('tɛtrəˌpɒdz; ) are four-limbed vertebrate animals constituting the superclass Tetrapoda (tɛ'træpədə). It includes all extant and extinct amphibians, and the amniotes which in turn evolved into the sauropsids (reptiles, including dinosaurs and therefore birds) and synapsids (extinct pelycosaurs, therapsids and all extant mammals). Some tetrapods such as snakes, legless lizards and caecilians had evolved to become limbless via mutations of the Hox gene, although some do still have a pair of vestigial spurs that are remnants of the hindlimbs. Tetrapods evolved from a clade of primitive semiaquatic animals known as the Tetrapodomorpha which, in turn, evolved from ancient lobe-finned fish (sarcopterygians) around 390 million years ago in the Middle Devonian period; their forms were transitional between lobe-finned fishes and true four-limbed tetrapods. Limbed vertebrates (tetrapods in the broad sense of the word) are first known from Middle

The evolution of lncRNA repertoires and expression patterns in tetrapods

Anamaria Necsulea, Magali Soumillon

Only a very small fraction of long noncoding RNAs (lncRNAs) are well characterized. The evolutionary history of lncRNAs can provide insights into their functionality, but the absence of lncRNA annotations in non-model organisms has precluded comparative analyses. Here we present a large-scale evolutionary study of lncRNA repertoires and expression patterns, in 11 tetrapod species. We identify approximately 11,000 primate-specific lncRNAs and 2,500 highly conserved lncRNAs, including approximately 400 genes that are likely to have originated more than 300 million years ago. We find that lncRNAs, in particular ancient ones, are in general actively regulated and may function predominantly in embryonic development. Most lncRNAs evolve rapidly in terms of sequence and expression levels, but tissue specificities are often conserved. We compared expression patterns of homologous lncRNA and protein-coding families across tetrapods to reconstruct an evolutionarily conserved co-expression network. This network suggests potential functions for lncRNAs in fundamental processes such as spermatogenesis and synaptic transmission, but also in more specific mechanisms such as placenta development through microRNA production.

Nature Publishing Group2014

Regulation of number and size of digits by posterior Hox genes: a dose-dependent mechanism with potential evolutionary implications

Denis Duboule, Xavier Warot, Jozsef Zakany

The proper development of digits, in tetrapods, requires the activity of several genes of the HoxA and HoxD homeobox gene complexes. By using a variety of loss-of-function alleles involving the five Hox genes that have been described to affect digit patterning, we report here that the group 11, 12, and 13 genes control both the size and number of murine digits in a dose-dependent fashion, rather than through a Hox code involving differential qualitative functions. A similar dose-response is observed in the morphogenesis of the penian bone, the baculum, which further suggests that digits and external genitalia share this genetic control mechanism. A progressive reduction in the dose of Hox gene products led first to ectrodactyly, then to olygodactyly and adactyly. Interestingly, this transition between the pentadactyl to the adactyl formula went through a step of polydactyly. We propose that in the distal appendage of polydactylous short-digited ancestral tetrapods, such as Acanthostega, the HoxA complex was predominantly active. Subsequent recruitment of the HoxD complex contributed to both reductions in digit number and increase in digit length. Thus, transition through a polydactylous limb before reaching and stabilizing the pentadactyl pattern may have relied, at least in part, on asynchronous and independent changes in the regulation of HoxA and HoxD gene complexes.

1997

Regulatory Switches Underlie Hoxd Gene Activation in Tetrapod Limbs

Guillaume Andrey

Accurate spatio-temporal control of Hox cluster genes expression is critical for the proper organization of body structures during vertebrate embryogenesis. In the limbs, Hoxd genes are critical in setting up the proximodistal and anteroposterior axes. Several studies have shown that long-range global regulatory elements are required to establish Hoxd genes expression territories in this tissue, via the co-regulation of several genes at once. Limb buds take their origin from the lateral plate mesoderm where the HoxD cluster is controlled by cues from the main body axis. During limb outgrowth Hoxd genes are then subjected to two subsequent activation waves: an early phase patterning proximal limb structures, arms and forearms and a late one instructing digits. As the late activation of Hoxd genes is known to rely upon a large regulatory archipelago located centromeric to the gene cluster, the control of the early phase remains poorly described (Montavon et al., 2011). In this work we show that the early activation domain requires a different, telomeric-located, regulatory landscape. This one megabase (Mb) large domain holds at least three regulatory regions contributing to Hoxd gene activation in early forelimb and hindlimb buds. To our surprise the abrogation of most of the early telomeric enhancers induced a dramatic decrease of central Hoxd transcription in forelimbs but only removed 50% of the transcripts in hindlimbs. This discrepancy most likely arises from the difference in the epigenetic status of the HoxD cluster in anterior and posterior limb fields where forelimb and hindlimb respectively take their origin. As the cluster does not possess the same fraction of active genes in these progenitors it most likely does not respond to early cues in the same way. In the second part of this work we noticed an unexpected decrease of the late expression phase in all mutants lacking early enhancers. This observation shows that digit progenitors have to implement the early phase in order to gain competence toward the late centromeric regulation. This transition between early and late regulations involves a set of central Hoxd genes, i.e. Hoxd11 to Hoxd9. To implement both regulations, these loci switch between two topological domains containing the centromeric and telomeric regulatory landscapes respectively (Dixon et al., 2012). The ability to switch from one domain to another depends on the relative position of genes towards the boundary between both domains and correlates with their respective expression. Moreover, the switch between both topological domains mechanically induces an intermediate, Hoxd-free zone, in-between the two expression phases that will later produce the mesopodium, the articulation between our arms and our hands.

EPFL2013

Regulatory Switches Underlie Hoxd Gene Activation in Tetrapod Limbs

Guillaume Andrey

EPFL2013