Genetic and developmental bases of serial homology in vertebrate limb evolution

Development ◽  
2000 ◽  
Vol 127 (24) ◽  
pp. 5233-5244 ◽  
Author(s):  
I. Ruvinsky ◽  
J.J. Gibson-Brown

Two sets of paired appendages are a characteristic feature of the body plan of jawed vertebrates. While the fossil record provides a good morphological description of limb evolution, the molecular mechanisms involved in this process are only now beginning to be understood. It is likely that the genes essential for limb development in modern vertebrates were also important players during limb evolution. In recent years, genes from a number of gene families have been described that play important roles both in limb induction and in later patterning processes. These advances facilitate inquiries into several important aspects of limb evolution such as their origin, position along the body axis, number and identity. Integrating paleontological, developmental and genetic data, we propose models to explain the evolution of paired appendages in vertebrates. Whereas previous syntheses have tended to focus on the roles of genes from a single gene family, most notably Hox genes, we emphasize the importance of considering the interactions among multiple genes from different gene families for understanding the evolution of complex developmental systems. Our models, which underscore the roles of gene duplication and regulatory ‘tinkering’, provide a conceptual framework for elucidating the evolution of serially homologous structures in general, and thus contribute to the burgeoning field seeking to uncover the genetic and developmental bases of evolution.

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Xing Wang ◽  
Yi Zhang ◽  
Yufeng Zhang ◽  
Mingming Kang ◽  
Yuanbo Li ◽  
...  

AbstractEarthworms (Annelida: Crassiclitellata) are widely distributed around the world due to their ancient origination as well as adaptation and invasion after introduction into new habitats over the past few centuries. Herein, we report a 1.2 Gb complete genome assembly of the earthworm Amynthas corticis based on a strategy combining third-generation long-read sequencing and Hi-C mapping. A total of 29,256 protein-coding genes are annotated in this genome. Analysis of resequencing data indicates that this earthworm is a triploid species. Furthermore, gene family evolution analysis shows that comprehensive expansion of gene families in the Amynthas corticis genome has produced more defensive functions compared with other species in Annelida. Quantitative proteomic iTRAQ analysis shows that expression of 147 proteins changed in the body of Amynthas corticis and 16 S rDNA sequencing shows that abundance of 28 microorganisms changed in the gut of Amynthas corticis when the earthworm was incubated with pathogenic Escherichia coli O157:H7. Our genome assembly provides abundant and valuable resources for the earthworm research community, serving as a first step toward uncovering the mysteries of this species, and may provide molecular level indicators of its powerful defensive functions, adaptation to complex environments and invasion ability.


2021 ◽  
Author(s):  
Guangyi Fan ◽  
Yaolei Zhang ◽  
Jiahao Wang ◽  
Meiqi Lv ◽  
Haoyang Gao ◽  
...  

Invertebrates, animals (metazoans) without backbones, encompass ~97% of all animal yet remains understudied. They have provided insights into molecular mechanisms underlying fundamentally identical mechanisms in phylogenetically diverse animals, including vertebrates. Marine invertebrates have long fascinated researchers due to their abundance, diversity, adaptations, and impact on ecosystems and human economies. Here, we report a compendium and appraisal of 190 marine invertebrate genomes spanning 21 phyla, 43 classes, 92 orders, and 134 families. We identify a high proportion and long unit size of tandem repeats, likely contributing to reported difficulties in invertebrate genome assembly. A well-supported phylogenetic tree of marine invertebrates from 974 single-copy orthologous genes resolved topological controversies. We show that Ctenophora is at the basal phylum and Porifera is the sister group of Parahoxozoa; that Xenacoelomorpha is within Bilateria and is the sister group to Protostomia, rejecting three out of four hypotheses in the field; and that Bryozoa is at the basal position of Lophotrochozoa, not grouped into Lophophorata. We also present insights into the genetic underpinnings of metazoans from Hox genes, innate immune gene families, and nervous system gene families. Our marine invertebrate genome compendium provides a unified foundation for studies on their evolution and effects on ecological systems and human life.


Development ◽  
2002 ◽  
Vol 129 (22) ◽  
pp. 5161-5170 ◽  
Author(s):  
Jennifer K. Ng ◽  
Yasuhiko Kawakami ◽  
Dirk Büscher ◽  
Ángel Raya ◽  
Tohru Itoh ◽  
...  

A major gap in our knowledge of development is how the growth and identity of tissues and organs are linked during embryogenesis. The vertebrate limb is one of the best models to study these processes. Combining mutant analyses with gain- and loss-of-function approaches in zebrafish and chick embryos, we show that Tbx5, in addition to its role governing forelimb identity,is both necessary and sufficient for limb outgrowth. We find thatTbx5 functions downstream of WNT signaling to regulateFgf10, which, in turn, maintains Tbx5 expression during limb outgrowth. Furthermore, our results indicate that Tbx5 andWnt2b function together to initiate and specify forelimb outgrowth and identity. The molecular interactions governed by members of the T-box,Wnt and Fgf gene families uncovered in this study provide a framework for understanding not only limb development, but how outgrowth and identity of other tissues and organs of the embryo may be regulated.


2018 ◽  
Author(s):  
Chloe Moreau ◽  
Paolo Caldarelli ◽  
Didier Rocancourt ◽  
Julian Roussel ◽  
Nicolas Denans ◽  
...  

SummaryLimb position along the body is highly consistent within one species but very variable among vertebrates. Despite major advances in our understanding of limb patterning in three dimensions, how limbs reproducibly form along the anteroposterior axis remains largely unknown. Hox genes have long been suspected to control limb position, however supporting evidences are mostly correlative and their role in this process remains unclear. Here we show that Hox genes determine the avian forelimb position in a two-step process: first, their sequential collinear activation during gastrulation controls the relative position of their own successive expression domains along the body axis. Then, within these collinear domains, Hox genes differentially activate or repress the genetic cascade responsible for forelimb initiation. Furthermore, we provide evidences that changes in the timing of collinear Hox gene activation might underlie natural variation in forelimb position between different birds. Altogether our results which characterize the cellular and molecular mechanisms underlying the regulation and natural variation of forelimb position in avians, show a direct and early role for Hox genes in this process.


Development ◽  
1996 ◽  
Vol 122 (4) ◽  
pp. 1175-1185 ◽  
Author(s):  
A.P. Davis ◽  
M.R. Capecchi

Using gene targeting in mice, we have undertaken a systematic mutational analysis of the homeobox-containing 5′ HoxD genes. In particular, we have characterized the limb defects observed in mice with independent targeted disruptions of hoxd-12 and hoxd-13. Animals defective for hoxd-12 are viable, fertile, and appear outwardly normal yet have minor autopodal defects in the forelimb which include a reduction in the bone length of metacarpals and phalanges, and a malformation of the distal carpal bone d4. The limb phenotypes observed in hoxd-13 mutant mice are more extensive, including strong reductions in length, complete absences, or improper segmentations of many metacarpal and phalangeal bones. Additionally, the d4 carpal bone is not properly formed and often produces an extra rudimentary digit. To examine the genetic interactions between the 5′ HoxD genes, we bred these mutant strains with each other and with our previously characterized hoxd-11 mouse to produce a series of trans-heterozygotes. Skeletal analyses of these mice reveal that these genes interact in the formation of the vertebrate limb, since the trans-heterozygotes display phenotypes not present in the individual heterozygotes, including more severe carpal, metacarpal and phalangeal defects. Some of these phenotypes appear to be accounted for by a delay in the ossification events in the autopod, which lead to either the failure of fusion or the elimination of cartilaginous elements. Characteristically, these mutations lead to the overall truncation of digits II and V on the forelimb. Additionally, some trans-animals show the growth of an extra postaxial digit VI, which is composed of a bony element resembling a phalange. The results demonstrate that these genes interact in the formation of the limb. In addition to the previously characterized paralogous interactions, a multitude of interactions between Hox genes is used to finely sculpt the forelimb. The 5′ Hox genes could therefore act as a major permissive genetic milieu that has been exploited by evolutionary adaptation to form the tetrapod limbs.


eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Tempei Sato ◽  
Kensuke Kataoka ◽  
Yoshiaki Ito ◽  
Shigetoshi Yokoyama ◽  
Masafumi Inui ◽  
...  

The body plan along the anteroposterior axis and regional identities are specified by the spatiotemporal expression of Hox genes. Multistep controls are required for their unique expression patterns; however, the molecular mechanisms behind the tight control of Hox genes are not fully understood. In this study, we demonstrated that the Lin28a/let-7 pathway is critical for axial elongation. Lin28a–/– mice exhibited axial shortening with mild skeletal transformations of vertebrae, which were consistent with results in mice with tail bud-specific mutants of Lin28a. The accumulation of let-7 in Lin28a–/– mice resulted in the reduction of PRC1 occupancy at the Hox cluster loci by targeting Cbx2. Consistently, Lin28a loss in embryonic stem-like cells led to aberrant induction of posterior Hox genes, which was rescued by the knockdown of let-7. These results suggest that the Lin28/let-7 pathway is involved in the modulation of the ‘Hox code’ via Polycomb regulation during axial patterning.


2019 ◽  
Author(s):  
Feini Qu ◽  
Ilan C. Palte ◽  
Paul M. Gontarz ◽  
Bo Zhang ◽  
Farshid Guilak

AbstractHumans have limited regenerative potential of musculoskeletal tissues following limb or digit loss. The murine digit has been used to study mammalian regeneration, where stem/progenitor cells (the ‘blastema’) regrow the digit tip after distal, but not proximal, amputation. However, the molecular mechanisms responsible for this response remain to be determined. We hypothesized that regeneration is initiated and maintained by a gene regulatory network that recapitulates aspects of limb development, whereas a non-regenerative response exhibits fibrotic wound healing and minimal bone remodeling. To test these hypotheses, we evaluated the spatiotemporal formation of bone and fibrous tissues after level-dependent amputation of the murine terminal phalanx and quantified the transcriptome of the repair tissue. We show that digit regeneration is a level-dependent and spatiotemporally controlled process, with distal and proximal amputations showing significant differences in gene expression and tissue regrowth over time. Regeneration is characterized by the transient upregulation of genes that direct skeletal system development and limb morphogenesis, including distal Hox genes. By identifying the molecular pathways regulating regeneration, this work will lead to novel therapies that restore complex tissues after injury.Summary StatementMurine digit tip regeneration after distal amputation is orchestrated through a transient, limb-specific gene network by blastema cells. Proximal amputation activates an alternate transcriptional program that results in scar formation.


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