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Danielle Dhouailly

Publications and source records attributed to Danielle Dhouailly.

14 recordsLinked to original sources
PubMed2005

Transdifferentiation of corneal epithelium into epidermis occurs by means of a multistep process triggered by dermal developmental signals.

Differentiated cells of the corneal epithelium are converted to hair, along with their associated stem cells, then interfollicular epidermis, by means of a multistep process triggered by dermal developmental signals. The committed basal cells of the adult corneal epithelium dedifferentiate under the control of signals from an associated embryonic hair-forming dermis, likely Wnts, and revert to a limbal basal cell phenotype. This initial process involves the down-regulation of Pax6 and the loss of expression of corneal-specific keratins and the induction of basal keratinocyte markers. These dedifferentiated cells are able to reinduce dermal condensations, which in turn induce the formation of hair follicles from cells that have lost Pax6 expression, by means of a Noggin-dependent mechanism. An epidermis is subsequently formed by cells derived from the newly segregated hair stem cells.

Animals↗
PubMed2004

Signaling dynamics of feather tract formation from the chick somatopleure.

In the chick, most feathers are restricted to specific areas of the skin, the feather tracts or pterylae, while other areas, such as the apteria, remain bare. In the embryo, the expansion and closure of the somatopleure leads to the juxtaposition of the ventral pteryla, midventral apterium and amnion. The embryonic proximal somatopleural mesoderm is determined to form a feather-forming dermis at 2 days of incubation (E2), while the embryonic distal and the extra-embryonic somatopleure remain open to determination. We found a progressive, lateral expression of Noggin in the embryonic area, and downregulation of Msx1, a BMP4 target gene, with Msx1 expression being ultimately restricted to the most distal embryonic and extra-embryonic somatopleural mesoderm. Msx1 downregulation thus correlates with the formation of the pterylae, and its maintenance to that of the apterium. Suspecting that the inhibition of BMP4 signaling might be linked to the determination of a feather-forming dermis, we grafted Noggin-expressing cells in the distal somatopleure at E2. This elicited the formation of a supplementary pteryla in the midventral apterium. Endogenous Noggin, which is secreted by the intermediate mesoderm at E2, then by the proximal somatopleure at E4, could be sufficient to suppress BMP4 signaling in the proximal somatopleural mesoderm and then in part of the distal somatopleure, thus in turn allowing the formation of the dense dermis of the future pterylae. The same result was obtained with the graft of Shh-producing cells, but Noggin and Shh are both required in order to change the future amnion into a feather-bearing skin. A possible synergistic role of endogenous Shh from the embryonic endoderm remains to be confirmed.

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PubMed2004

Dorsal versus ventral scales and the dorsoventral patterning of chick foot epidermis.

The dorsal and ventral scales of the chick foot can be distinguished morphologically and molecularly: the dorsal oblong overlapping scuta expressing both alpha and beta keratins, and the ventral roundish nonprotruding reticula expressing only alpha keratins. The question arises how En-1 and Lmx1, whose role in dorsoventral limb patterning has been well established, can affect skin morphogenesis, which occurs 8 to 12 days later. Forced expression of En-1 or of Lmx1 in the hindlimb have, respectively, as expected, a ventralizing or a dorsalizing effect on skin, leading to the formation of either reticula-type or scuta-type scales on both faces. In both cases, however, the scales are abnormal and even glabrous skin without any scales at all may form. The normal inductive interactions between dermis and epidermis are disturbed after En-1 or Lmx1 misexpression. Effectively, while Lmx1 endows the dermal precursors of the ventral region with scuta inducing ability, En-1 blocks the competence of the dorsal epidermis to build scuta.

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PubMed2004

Transformation of amnion epithelium into skin and hair follicles.

There is increasing interest into the extent to which epithelial differentiation can be altered by mesenchymal influence, and the molecular basis for these changes. In this study, we investigated whether amnion epithelium could be transformed into skin and hair follicles by associating E12.5 to E14.5 mouse amnion from the ROSA 26 strain, with mouse embryonic hair-forming dermis from a wild-type strain. These associations were able to produce fully formed hair follicles with associated sebaceous glands, and skin epidermis. Using beta-galactosidase staining we were able to demonstrate that the follicular epithelium and skin epidermis, but not the associated dermal cells, originated from the amnion. As Noggin and Sonic hedgehog (Shh) were recently shown to be required for early chick ventral skin formation, and able to trigger skin and feather formation from chick amnion, we associated cells engineered to produce those two factors with mouse amnion. In a few cases, we obtained hair buds connected to a pluristratified epithelium; however, the transformation of the amnion was impeded by uncontrolled fibroblastic proliferation. In contrast to an earlier report, none of our control amnion specimens autonomously transformed into skin and hair follicles, indicating that specific influences are necessary to elicit follicle formation from the mouse amnion. The ability to turn amnion into skin and its appendages has practical potential for the tissue engineering of replacement skin, and related biotechnological approaches.

Amnion↗
PubMed2004

Molecular mechanisms controlling dorsal dermis generation from the somitic dermomyotome.

The initiation of the development of skin appendages (hair/feathers/scales) requires a signal from the competent dense dermis to the epidermis (Dhouailly, 1977). It is therefore essential to understand how to make a competent dermis. In recent years, a few studies have focused on the development of the dorsal dermis from the somitic dermomyotome. Our first aim in this review is to attempt to reconcile the available data on the origin of the dorsal dermis and summarize the present knowledge on the molecular mechanisms implicated in dermal lineage induction. Secondly, we open the discussion on the formation of a loose pre-dermal mesenchyme and more importantly of a dense dermis capable of participating in appendage development. To go further we draw a comparison between the chick and mouse systems to gain a new insight into how to initiate appendage morphogenesis and regulate the extent of hair/feather fields.

Animals↗
PubMed2004

The different steps of skin formation in vertebrates.

Skin morphogenesis occurs following a continuous series of cell-cell interactions which can be subdivided into three main stages: 1- the formation of a dense dermis and its overlying epidermis in the future appendage fields (macropattern); 2- the organization of these primary homogeneous fields into heterogeneous ones by the appearance of cutaneous appendage primordia (micropattern) and 3- cutaneous appendage organogenesis itself. In this review, we will first show, by synthesizing novel and previously published data from our laboratory, how heterogenetic and heterospecific dermal/epidermal recombinations have allowed us to distinguish between the respective roles of the dermis and the epidermis. We will then summarize what is known from the work of many different research groups about the molecular signaling which mediates these interactions in order to introduce the following articles of this Special Issue and to highlight what remains to done.

Animals↗
PubMed2004

How and when the regional competence of chick epidermis is established: feathers vs. scutate and reticulate scales, a problem en route to a solution.

Most of the chick body is covered with feathers, while the tarsometatarsus and the dorsal face of the digits form oblong overlapping scales (scuta) and the plantar face rounded nonoverlapping scales (reticula). Feathers and scuta are made of beta-keratins, while the epidermis of reticula and inter-appendage or apteria (nude regions) express a-keratins. These regional characteristics are determined in skin precursors and require an epidermal FGF-like signal to be expressed. Both the initiation of appendages, their outline and pattern depend on signals from the dermis, while their asymmetry and outgrowth depend on epidermal competence. For example, the plantar dermis of the central foot pad induces reticula in a plantar or feathers in an apteric epidermis, in a hexagonal pattern starting from the medial point. By manipulating Shh levels in the epidermis, the regional appendage type can be changed from scuta or reticula to feather, whereas the inhibition of Wnt7a, together with a downregulation of Shh gives rise to reticula and in extreme cases, apteria. During morphogenesis of plantar skin, the epidermal expression of En-1, acting as a repressor both of Wnt7a and Shh, is linked to the formation of reticula. Finally, in birds, the complex formation of feathers, which can be easily triggered, even in the extra-embryonic somatopleure, may result from a basic genetic program, whereas the simple formation of scales appears secondarily derived, as requiring a partial (scuta) or total (reticula) inhibition of epidermal outgrowth and beta-keratin gene expression, an inhibition lost for the scuta in the case of feathered feet breeds.

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PubMed2004

Skin field formation: morphogenetic events.

This chapter is mostly a review of the pioneering work of the Philippe Sengel school in Grenoble carried out in the late sixties and the seventies. The questions raised concerning the morphogenesis of feather tracts were approached by means of microsurgery on chick embryos. P. Sengel and his wife M. Kieny had the feeling that proteins synthesized by the neural tube were required for the formation of feather fields. It was my pleasure to carry on the story from the beginning. Although some clarifications concerning this morphogenesis have been contributed by my group and by a few other laboratories interested in this subject, the most important contributions to recent research have been the elucidation of the nature of the required messages, which will be explored further in other papers in this Issue.

Amnion↗
PubMed2004

Ventral vs. dorsal chick dermal progenitor specification.

The dorsal and the ventral trunk integuments of the chick differ in their dermal cell lineage (originating from the somatic and somatopleural mesoderm respectively) and in the distribution of their feather fields. The dorsal macropattern has a large spinal pteryla surrounded by semi-apteria, whereas the ventral skin has a true medial apterium surrounded by the ventral pterylae. Comparison of the results of heterotopic transplantations of distal somatopleure in place of somatic mesoderm (Mauger 1972) or in place of proximal somatopleure (our data), leads to two conclusions. These are that the fate of the midventral apterium is not committed at day 2 of incubation and that the signals from the environment which specify the ventral and dorsal featherforming dermal progenitors are different. Effectively, Shh, but not Wnt -1 signalling can induce the formation of feather forming dermis from the embryonic somatopleure. Shh is not able, however, to trigger the formation of a feather forming dermis from the extra embryonic somatopleure. This brief report constitutes the first attempt, by comparing old and new preliminary results, to understand whether dermal progenitors at different sites are specified by different signalling pathways.

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PubMed2004

Transdifferentiation of corneal epithelium: evidence for a linkage between the segregation of epidermal stem cells and the induction of hair follicles during embryogenesis.

Corneal epithelium transdifferentiation into a hair-bearing epidermis provides a particularly useful system for studying the possibility that transient amplifying (TA) cells are able to activate different genetic programs in response to a change in their fibroblast environment, as well as to follow the different steps of rebuilding an epidermis from induced stem cells. Corneal stem and TA cells are found in different locations - stem cells at the periphery, in the limbus, and TA cells more central. Moreover, the TA cells already express the differentiating corneal-type keratin pair K3/K12, whereas the limbal keratinocytes express the basal keratin pair K5/K14. In contrast, suprabasal epidermal keratinocytes express keratin pair K1-2/K10, and basal keratinocytes the keratin pair K5/K14. The results of tissue recombination experiments show that adult central corneal cells are able to respond to specific information originating from embryonic dermis. First, the cells located at the base of the corneal epithelium show a decrease in expression of K12 keratin, followed by an increase in K5 expression; they then proliferate and form hair follicles. The first K10 expressing cells appear at the junction of the new hair follicles and the covering corneal epithelium. Their expansion finally gives rise to epidermal strata, which displace the corneal suprabasal keratinocytes. Corneal TA cells can thus be reprogrammed to form epidermal cells, first by reverting to a basal epithelial-type, then to hair pegs and probably concomitantly to hair stem cells. This confirms the role of the hair as the main reservoir of epidermal stem cells and raises the question of the nature of the dermal messages which are both involved in hair induction and stem cell specification.

Animals↗
PubMed2003

Hair follicle stem cells.

The workshop on Hair Follicle Stem Cells brought together investigators who have used a variety of approaches to try to understand the biology of follicular epithelial stem cells, and the role that these cells play in regulating the hair cycle. One of the main concepts to emerge from this workshop is that follicular epithelial stem cells are multipotent, capable of giving rise not only to all the cell types of the hair, but also to the epidermis and the sebaceous gland. Furthermore, such multipotent stem cells may represent the ultimate epidermal stem cell. Another example of epithelial stem cell and transit amplifying cell plasticity, was the demonstration that adult corneal epithelium, under the influence of embryonic skin dermis could form an epidermis as well as hair follicles. With regards to the location of follicular epithelial stem cells, immunohistochemical and ultrastructural data was presented, indicating that cells with stem cell attributes were localized to the prominent bulge region of developing human fetal hair follicles. Finally, a new notion was put forth concerning the roles that the bulge-located stem cells and the hair germ cells played with respect to the hair cycle.

Animals↗
PubMed2002

Differential regulation of the chick dorsal thoracic dermal progenitors from the medial dermomyotome.

The chick dorsal feather-forming dermis originates from the dorsomedial somite and its formation depends primarily on Wnt1 from the dorsal neural tube. We investigate further the origin and specification of dermal progenitors from the medial dermomyotome. This comprises two distinct domains: the dorsomedial lip and a more central region (or intervening zone) that derives from it. We confirm that Wnt1 induces Wnt11 expression in the dorsomedial lip as previously shown, and show using DiI injections that some of these cells, which continue to express Wnt11 migrate under the ectoderm, towards the midline, to form most of the dorsal dermis. Transplantation of left somites to the right side to reverse the mediolateral axis confirms this finding and moreover suggests the presence of an attractive or permissive environment produced by the midline tissues or/and a repellent or inadequate environment by the lateral tissues. By contrast, the dorsolateral dermal cells just delaminate from the surface of the intervening space, which expresses En1. Excision of the axial organs or the ectoderm, and grafting of Wnt1-secreting cells, shows that, although the two populations of dermal progenitors both requires Wnt1 for their survival, the signalling required for their specification differs. Indeed Wnt11 expression relies on dorsal neural tube-derived Wnt1, while En1 expression depends on the presence of the ectoderm. The dorsal feather-forming dermal progenitors thus appear to be differentially regulated by dorsal signals from the neural tube and the ectoderm, and derive directly and indirectly from the dorsomedial lip. As these two dermomyotomal populations are well known to also give rise to epaxial muscles, an isolated domain of the dermomyotome that contains only dermal precursors does not exist and none of the dermomyotomal domains can be considered uniquely as a dermatome.

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