Limb development in the Pacific giant salamanders, Dicamptodon (Amphibia, Caudata, Dicamptodontidae)

1998 ◽  
Vol 76 (11) ◽  
pp. 2058-2066 ◽  
Author(s):  
David B Wake ◽  
Neil Shubin

The larvae of Pacific giant salamanders, Dicamptodon (Dicamptodontidae), develop in streams, display precocious limb development, and possess a full complement of digits at hatching. Limb morphogenesis was studied using cleared whole mounts stained with Alcian Blue or by immunohistochemical methods to reveal stages of limb development. Limb morphogenesis in these salamanders conforms to the general caudate pattern, i.e., preaxial dominance and precocious development of an initially isolated digital arch, despite some differences in detail from other salamander taxa. These comparisons support the hypothesis that a fundamental ground plan characterizes limb development in salamanders which transcends adaptive modifications related to ecology and life-history evolution. This ground plan differs from that which characterizes frogs and amniotes, which shows postaxial dominance and a digital arch that arises from basal elements.

Development ◽  
1996 ◽  
Vol 122 (5) ◽  
pp. 1385-1394 ◽  
Author(s):  
J.A. Helms ◽  
C.H. Kim ◽  
G. Eichele ◽  
C. Thaller

In the chick limb bud, the zone of polarizing activity controls limb patterning along the anteroposterior and proximodistal axes. Since retinoic acid can induce ectopic polarizing activity, we examined whether this molecule plays a role in the establishment of the endogenous zone of polarizing activity. Grafts of wing bud mesenchyme treated with physiologic doses of retinoic acid had weak polarizing activity but inclusion of a retinoic acid-exposed apical ectodermal ridge or of prospective wing bud ectoderm evoked strong polarizing activity. Likewise, polarizing activity of prospective wing mesenchyme was markedly enhanced by co-grafting either a retinoic acid-exposed apical ectodermal ridge or ectoderm from the wing region. This equivalence of ectoderm-mesenchyme interactions required for the establishment of polarizing activity in retinoic acid-treated wing buds and in prospective wing tissue, suggests a role of retinoic acid in the establishment of the zone of polarizing activity. We found that prospective wing bud tissue is a high-point of retinoic acid synthesis. Furthermore, retinoid receptor-specific antagonists blocked limb morphogenesis and down-regulated a polarizing signal, sonic hedgehog. Limb agenesis was reversed when antagonist-exposed wing buds were treated with retinoic acid. Our results demonstrate a role of retinoic acid in the establishment of the endogenous zone of polarizing activity.


Development ◽  
1992 ◽  
Vol 116 (2) ◽  
pp. 289-296 ◽  
Author(s):  
C.J. Tabin

Limb development has long been a model system for studying vertebrate pattern formation. The advent of molecular biology has allowed the identification of some of the key genes that regulate limb morphogenesis. One important class of such genes are the homeobox-containing, or Hox genes. Understanding of the roles these genes play in development additionally provides insights into the evolution of limb pattern. Hox gene expression patterns divide the embryonic limb bud into five sectors along the anterior/posterior axis. The expression of specific Hox genes in each domain specifies the developmental fate of that region. Because there are only five distinct Hox-encoded domains across the limb bud there is a developmental constraint prohibiting the evolution of more than five different types of digits. The expression patterns of Hox genes in modern embryonic limb buds also gives clues to the shape of the ancestral fin field from which the limb evolved, hence elucidating the evolution of the tetrapod limb.


Development ◽  
1997 ◽  
Vol 124 (6) ◽  
pp. 1109-1117 ◽  
Author(s):  
D. Macias ◽  
Y. Ganan ◽  
T.K. Sampath ◽  
M.E. Piedra ◽  
M.A. Ros ◽  
...  

Bone Morphogenetic Protein 2 (BMP-2) and Osteogenic Protein 1 (OP-1, also termed BMP-7) are members of the transforming growth factor beta superfamily. In the present study, we have analyzed the effects of administering them locally at different stages and locations of the chick limb bud using heparin beads as carriers. Our results show that these BMPs are potent apoptotic signals for the undifferentiated limb mesoderm but not for the ectoderm or the differentiating chondrogenic cells. In addition, they promote intense radial growth of the differentiating cartilages and disturb the formation of joints accompanied by alterations in the pattern of Indian hedgehog and ck-erg expression. Interestingly, the effects of these two BMPs on joint formation were found to be different. While the predominant effect of BMP-2 is alteration in joint shape, OP-1 is a potent inhibitory factor for joint formation. In situ hybridizations to check whether this finding was indicative of specific roles for these BMPs in the formation of joints revealed a distinct and complementary pattern of expression of these genes during the formation of the skeleton of the digits. While Op-1 exhibited an intense expression in the perichondrium of the developing cartilages with characteristic interruptions in the zones of joint formation, Bmp-2 expression was a positive marker for the articular interspaces. These data suggest that, in addition to the proposed role for BMP-2 and OP-1 in the establishment of the anteroposterior axis of the limb, they may also play direct roles in limb morphogenesis: (i) in regulating the amount and spatial distribution of the undifferentiated prechondrogenic mesenchyme and (ii) in controlling the location of the joints and the diaphyses of the cartilaginous primordia of the long bones once the chondrogenic aggregates are established.


Development ◽  
1997 ◽  
Vol 124 (18) ◽  
pp. 3493-3500 ◽  
Author(s):  
Y. Herault ◽  
N. Fraudeau ◽  
J. Zakany ◽  
D. Duboule

Ulnaless (Ul), an X-ray-induced dominant mutation in mice, severely disrupts development of forearms and forelegs. The mutation maps on chromosome 2, tightly linked to the HoxD complex, a cluster of regulatory genes required for proper morphogenesis. In particular, 5′-located (posterior) Hoxd genes are involved in limb development and combined mutations within these genes result in severe alterations in appendicular skeleton. We have used several engineered alleles of the HoxD complex to genetically assess the potential linkage between these two loci. We present evidence indicating that Ulnaless is allelic to Hoxd genes. Important modifications in the expression patterns of the posterior Hoxd-12 and Hoxd-13 genes at the Ul locus suggest that Ul is a regulatory mutation that interferes with a control mechanism shared by multiple genes to coordinate Hoxd function during limb morphogenesis.


Development ◽  
1971 ◽  
Vol 26 (2) ◽  
pp. 169-179
Author(s):  
D. Tarin ◽  
A. P. Sturdee

This investigation has used histological techniques and the scanning electron microscope to establish the presence of an apical ectodermal ridge in the developing limbs of Xenopus laevis. The ridge appeared at stage 50, reached its maximal size at stage 51, and subsequently disappeared by stage 53. The course of the ridge was consistently related to a marginal sinus in the underlying mesenchyme. The other features of limb morphogenesis, such as the formation of a paddle and the sequence of condensation of skeletal rudiments in the mesenchyme, corresponded closely to those seen in other vertebrates. It remains to be seen whether the ridge we have demonstrated in Xenopus exercises a similar function to that claimed for its counterpart in the chick.


Development ◽  
1994 ◽  
Vol 1994 (Supplement) ◽  
pp. 181-186
Author(s):  
Bruce A. Morgan ◽  
Cliff Tabin

In recent years, molecular analysis has led to the identification of some of the key genes that control the morphogenesis of the developing embryo. Detailed functional analysis of these genes is rapidly leading to a new level of understanding of how embryonic form is regulated. Understanding the roles that these genes play in development can additionally provide insights into the evolution of morphology. The 5′ genes of the vertebrate Hox clusters are expressed in complex patterns during limb morphogenesis. Various models suggest that the Hoxd genes specify positional identity along the anteroposterior (A-P) axis of the limb. Close examination of the pattern of Hoxd gene expression in the limb suggests that a distinct combination of Hoxd gene expressed in different digit primordia is unlikely to specify each digit independently. The effects of altering the pattern of expression of the Hoxd-11 gene at different times during limb development indicate that the Hoxd genes have separable early and late roles in limb morphogenesis. In their early role, the Hoxd genes are involved in regulating the growth of the undifferentiated limb mesenchyme. Restriction of the expression of successive 5′ Hoxd genes to progressively more posterior regions of the bud results in the asymmetric outgrowth of the limb mesenchyme. Later in limb development, Hoxd genes also regulate the maturation of the nascent skeletal elements. The degree of overlap in function between different Hoxd genes may be different in these early and late roles. The combined action of many Hox genes on distinct developmental processes contribute to pattern asymmetry along the A-P axis.


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.


PMLA ◽  
1935 ◽  
Vol 50 (4) ◽  
pp. 1373-1374

The thirty-seventh annual meeting of the Philological Association of the Pacific Coast was held at Stanford University, California, on November 29 and 30, 1935.


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