![]() rerio transgenic embryos, the regulatory activity of conserved elements associated to genes involved in developmental control among different chordates (Homo sapiens and Danio rerio for vertebrates, Ciona robusta and Ciona savignyi for tunicates and Branchiostoma floridae for cephalochordates). We used a comparative approach to facilitate the identification of CNEs among distantly related or highly divergent species and experimentally demonstrated the functional significance of these novel CNEs. Nevertheless, the high divergent rate of genomic sequences of several organisms, such as tunicates, complicates the characterization of these conserved elements and very few examples really may prove their functional activity. ![]() A combination of bioinformatics and experimental approaches can be used to identify CNEs with regulatory activity in phylogenetically distant species. The distribution of these conserved non-coding elements (CNE) within and across genomes has suggested that many of them may have roles as transcriptional regulatory elements. Non-coding regions with dozens to several hundred base pairs of extreme conservation have been found in all metazoan genomes. Our results highlight the importance of genomic analysis in the identification of disease-causing mutations and support crowdfunding as a means to fund low-budget projects and as a platform for scientific communication. We communicated the progress of this project to a large online audience, detailing the 'inner workings' of personalized whole genome sequencing with the aim of improving genetic literacy. We discovered that Lil BUB is affected by two distinct mutations: a heterozygous mutation in the limb enhancer of the Sonic hedgehog gene, previously associated with polydactyly in Hemingway cats and a novel homozygous frameshift deletion affecting the TNFRSF11A (RANK) gene, which has been linked to osteopetrosis in humans. Here, we used crowdfunding as an alternative funding source to sequence the genome of Lil BUB, a celebrity cat affected by rare disease phenotypes characterized by supernumerary digits, osteopetrosis and dwarfism, all phenotypic traits that also occur in human patients. The development of next-generation sequencing and its decreasing costs promises to alleviate such issues by supplying personal genomic information at a moderate price. Rare diseases and their underlying molecular causes are often poorly studied, posing challenges for patient diagnosis and prognosis. Comparative studies in different vertebrate species have shown that their morphogenetic activity is repetitively used to orchestrate the progressive specification of the eye with evolutionary conserved mechanisms that have been adapted to match the specific need of a given species. ![]() Here, we discuss the contribution of the Hh, Wnt, FGF, and BMP signaling pathways to the early patterning of the retina. These programs are driven by the interplay of signaling pathways and transcription factors, which progressively dictate how each tissue should evolve. These fundamental steps that enable the subsequent development of a functional eye, entail the precise coordination among genetic programs. During these early morphogenetic events, the optic vesicle is patterned along three different axes-proximo-distal, dorso-ventral, and naso-temporal-and three major domains: the neural retina, the retinal pigment epithelium (RPE), and the optic stalk. For permissions, please email: primordium of the vertebrate eye is composed of a pseudostratified and apparently homogeneous neuroepithelium, which folds inward to generate a bilayered optic cup. Mapping of active regulatory regions across lineages will shed new light on the evolutionary forces stabilizing ancestral developmental programs, as well as allowing their variation to sustain morphological adaptations on the inherited vertebrate body plan. This pioneer work, primarily centered in the mammalian lineage, has set the groundwork for further studies in representative vertebrate and chordate species. Here, I review recent comparative genomic and epigenomic studies, based on ChIP-seq and chromatin accessibility, which focus on the identification of functionally equivalent cis-regulatory modules among species. Inferring the evolutionary history of the group requires understanding the architecture of the developmental programs that constrain the vertebrate anatomy. Vertebrates, as most animal phyla, originated >500 million years ago during the Cambrian explosion, and progressively radiated into the extant classes.
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