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Melanocyte precocious differentiation and ectopic localization in Notch conditional loss-of-function mice.

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HAL Id: hal-02818814

https://hal.inrae.fr/hal-02818814

Submitted on 6 Jun 2020

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Melanocyte precocious differentiation and ectopic localization in Notch conditional loss-of-function mice.

Geneviève Aubin Houzelstein, J. Djian-Zaouche, Florence Bernex, Stéphanie Gadin, Virginie Delmas, Jean-Jacques Panthier

To cite this version:

Geneviève Aubin Houzelstein, J. Djian-Zaouche, Florence Bernex, Stéphanie Gadin, Virginie Delmas, et al.. Melanocyte precocious differentiation and ectopic localization in Notch conditional loss-of- function mice.. 13th meeting of the European Society for Pigment Cell Research, Sep 2006, Barcelone, Spain. pp.1, 2007. �hal-02818814�

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Melanocyte precocious differentiation and ectopic localization in Notch conditional loss-of-function mice G. Aubin-Houzelstein (1,2), J. Djian-Zaouche (1), F. Bernex (2), N. S. Gadin (2), V. Delmas (3) and J-J. Panthier (1, 2)

1. Mouse functional Genetics Unit, Institut Pasteur, 25 rue du Docteur Roux, 75724 Paris cedex 15, France.

2. Cellular and Molecular Genetics UMR955 INRA, ENVA, Ecole Nationale Vétérinaire d’Alfort, 7 avenue du Général-de-Gaulle, 94704 Maisons-Alfort cedex, France.

3. Developmental Genetics of Melanocytes, UMR146 CNRS-Institut Curie, Centre Universitaire, Orsay, France.

Notch signalling is essential to maintain a number of stem cell populations, including melanocyte stem cells (MSC).

Here, we re-investigate the phenotype of Tyr-Cre; RBPJkf/f conditional loss-of-function (cRBP-J KO) mice. We compared X-gal positive (X-gal +) cells distribution in skin from Tg(Dct-lacZ); cRBP-J KO and Tg(Dct-lacZ)control littermates from E12.5 onwards. Absence of Notch signalling did not impair melanocyte lineage development until E16.5. From E16.5 onwards, there was a slight reduction in the number of X-gal + melanoblasts in Tg(Dct-lacZ);

cRBP-J KO skin. We investigated melanocyte lineage distribution in postnatal hair follicles (HF). For this purpose, we counted X-gal + cells in the upper permanent portion (UPP), the lower permanent portion (LPP), and the upper transitory portion (UTP) of Tg(Dct-lacZ); cRBP-J KO and control anagen HF at P8 and P30. In Tg(Dct-lacZ); cRBP-J KO P8 and P30 HF, the average number of X-gal + cells per hair follicle was reduced and the distribution of X-gal + cells was impaired compared to control HF. Whereas the number of X-gal + cells remained constant between P8 and P30 in controls, it was drastically reduced in Tg(Dct-lacZ); cRBP-J KO LPP and UTP at P30 compared to P8.

Furthermore, in Tg(Dct-lacZ); cRBP-J KO HF, there were numerous pigmented X-gal + cells, mostly in LPP, but also in UPP and UTP; some were found in ectopic localizations: outside the outer root sheath, around the hair shaft, within the dermal papilla. A majority of Tg(Dct-lacZ); cRBP-J KO hair bulbs contained X-gal + cells that were not pigmented; the corresponding hairs were mostly grey or black at P8, and white at P30.

We conclude from these observations that in the LPP, Notch deficient MCS and/or transit amplifying melanoblasts undergo precocious differentiation leading to MCS pool depletion and reduced melanoblast number in the UTP; at the opposite, in the hair bulb, Notch deficient melanoblasts fail to differentiate into mature melanocytes.

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