[Epub ahead of print] 2: Zuzarte-Luis V, Montero JA, Torre-Perez N, Garcia-Porrero JA, Hurle JM. Cathepsin D gene expression outlines the areas. Epub Jun S(10), McGee H(11), Mendes M(12), Niebauer J(13), Pogosova N(14), Garcia-Porrero E(15), Rauch B(16), Schmid JP(17), Giannuzzi P(2). Dev Biol. Oct 1;(1) Epub Jun PubMed PMID: 3: Lorda-Diez CI, Montero JA, Choe S, Garcia-Porrero JA, Hurle JM. Ligand-.

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[Epub ahead of print] PubMed PMID: Rauch B, Ambrosetti M, Braga SS, Beckers P, Bussotti M, Faggiano P, Garcia-Porrero E, Kouidi E, Lamotte M. [Epub ahead of print] PubMed PMID: Epub Jan . Braga SS, Beckers P, Bussotti M, Faggiano P, Garcia-Porrero E, Kouidi E, Lamotte M. 1: García-García I, Hernández-González I, Díaz-Machado A, 2: Sarduy MR, García I, Coca MA, Perera A, Torres LA, Valenzuela CM, Epub Apr . Pérez-Oliva JF, Casanova-González M, García-García I, Porrero-Martín PJ.

Initial expression of Sox9 occupies the whole central region of the early bud Figures 1N,O. Regionalization of this domain in stylopod, zeugopod and digital arch is due to the loss of transcripts from the central region at Due to this process, expression of Sox9 appears as a loop where the distal curved region constitutes the digital arch.

The proximal part of the loop lengthens marking the position of the stylopod. The zeugopodial elements are identified as the lateral regions of the loop. In next stages the digit primordia appear as elongated domains of intensified Sox9 gene expression Figures 1R,S. Digits 3 and 4 are the first to appear. The skeletal domains of Sox9 in the Mauremys turtle are similar in fore and hind-limbs Figure 2.

At the beginning, a central ill-defined domain is transformed into a triangular domain with a posterior elongated vertex, which marks the stylopod Figure 2C.

The sides of the triangle form the zeugopodial domains, and the base corresponds with the digital arch.

The expression of Sox9 in the digital arch becomes progressively intensified at discrete regions to form digit primordia Figures 2D,E.

Digits 3 and 4 are the most precociously identifiable while digit 1 is the last to appear, preceded by digit 5 Figures 2E—I. In the course of digit development, the expression of Sox9 is progressively restricted to the digit tip and to the developing joints Figures 2E—I. Sox9 expression during limb development in the turtle Mauremys Leprosa.

Stages were established according to the developmental series of Yntema A,B adult limb in a live picture A and a radiographic image B to illustrate the presence of interdigital membranes in this species. J—L Comparative analysis of Sox9 expression in chick and duck interdigits.


J,K Sox9 expression in the chicken and duck autopod at day 6. L QPCR comparison of Sox9 expression level in the developing third interdigit of the leg bud of chicken white bars and duck gray bars embryos at equivalent developmental stages.

Incubation days id from left to right: chicken id 6.

Remarkably, the Mauremys turtle interdigital regions retain considerable levels of Sox9 expression not observed in chick and mouse embryos Figures 2F—I. To ascertain if interdigital expression of Sox9 associates with the absence of interdigit remodeling in the Mauremys turtle Figure 2A , we compared the level of expression of Sox9 in the third interdigit of the leg bud of chick and duck embryos, as characteristic models of species with free and webbed digits respectively.

As shown in Figures 2J—L , expression of Sox9 in the non-regressing interdigit of the duck was much higher than that of the chick embryo. Detailed analysis of phylogenetically related but phenotypically different species have provided important cues about the mechanisms accounting for limb morphogenesis Moore et al. Gene expression computational modeling have also provided insights on the molecular bases responsible for differences in limb skeletogenesis among vertebrates Uzkudun et al.

In all species, the expression of Sox9 marks the successive appearance of the stylopod, zeugopod, and autopod along the proximo-distal axis of the limb. The formation and expansion of the digit arch in the chick embryo is clearly distinct from that observed in mouse and turtle embryos.

Consistent with the evolutionary model proposed by Shubin and Alberch , in the avian limb the progressive appearance of the digit expression domains follows a polarized sequence from posterior to anterior, which is more accentuated in the wing bud.

In contrast, the digital arch domain in mouse and turtle limbs appears occupying a central position in the autopod, and in the course of development expands uniformly to the margins of the bud.

The consideration of such identities have implications for evolutionary hypothesis that consider digit 1, as the most distal element of a conserved skeletal axis modified in the course of evolution through branching and segmentation processes see Cohn et al.

Sox9 expression domains precede the appearance of prechondrogenic blastemas that were formerly employed in traditional comparative embryonic studies.

Hence, the differences among species observed here, support mechanisms of skeletal diversification based on the combination of a distinct distribution of signals with differences in the intrinsic properties of the skeletal progenitors of the autopod, likely associated with differential epigenetic signatures Sheth et al.

Both in the wing and in the leg of avian embryos, digits are different along the antero-posterior axis justifying the consideration of different digit identities according to their position and number of phalanxes.

In contrast, digits of mouse and turtle embryos, expands from the centrally located digital arch toward the margins of the limb bud. In this model of digit arch expansion, there are not morphological landmarks that allow to assign specific identities to the central digits 2,3,4. Therefore, at these embryonic stages mesopodial domains cannot be taken as a primary reference to establish the identity of the digits.

The only morphological differences observed among the pre-cartilaginous blastemas are located in the marginal digits digits 1 and 5 where Sox9 domains exhibit a reduced size and appear at more advanced stages than the central digits.

The growth of the limb bud is regulated by a complex signaling network Uzkudun et al. Consistent with our interpretation, central digits in these mutants, regardless of its number, are identical and indistinguishable from each other Norrie et al. These findings make plausible that digit formation result of the self-organization of the limb mesenchyme Cooper, , within an autopod of dimensions and shape finely tuned by regulatory genes responsible for growth Zhu et al. These signals are themselves closely regulated by the AER and the ZPA, to establish the pattern of limb skeletogenesis as well as the number of digits in the autopod.

FGFs inhibit chondrogenesis but expand the amount of Sox 9 positive skeletal progenitors and its overexpression in the limb results in the formation of extra cartilages, including extra-digits Montero et al.

RA is a potent inhibitor of Sox9 gene expression Weston et al. Hence, the pattern of Sox9 gene expression may reflect differences in the spatial distribution of signals within the limb bud mesoderm. Expression of Sox8, Sox9 and Sox10 in the developing valves and autonomic nerves of the embryonic heart. Mech Dev. Comparative analysis of the expression and regulation of Wnt5a, Fz4, and Frzb1 during digit formation and in micromass cultures. Dev Dyn. Stem cell emergence and hemopoietic activity are incompatible in mouse intraembryonic sites.


J Exp Med. Antigenic profiles of endothelial and hemopoietic lineages in murine intraembryonic hemogenic sites.

Dev Comp Immunol. A1 demonstrates restricted tissue distribution during embryonic development and functions to protect against cell death.

Am J Pathol. Potential intraembryonic hemogenic sites at pre-liver stages in the mouse.

Anat Embryol Berl. Initiation of hemopoiesis in the mouse embryo.

Ann N Y Acad Sci. Developmental events from hemopoietic stem cells to B-cell populations and Ig repertoires. Immunol Rev. No abstract available.

Enrique Marco de Lucas

Para-aortic splanchnopleura from early mouse embryos contains B1a cell progenitors. Basement membrane alterations during development and regression of tubular cysts. Kidney Int. Structural and morphometric characteristics of the basement membrane of rabbit parietal podocytes induced by corticoids.

Acta Anat Basel.

Arterial segmentation and subsegmentation in the human spleen. Histochemical characteristics of the basement membranes of the parietal podocytes in the rabbit kidney.

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A light- and electron-microscopic study. Retinal cell death occurs in the absence of retinal disc invagination: experimental evidence in papaverine-treated chicken embryos.Oria J.

Back to home page Return to top. Sox9 overexpression promotes polydactyly Akiyama et al. Neurosurgery Foix-Chavany-Marie Syndrome caused by a disconnection between the right pars opercularis of the inferior frontal gyrus and the supplementary motor area.

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