Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Dkk4 and Eda regulate distinctive developmental mechanisms for subtypes of mouse hair

ABSTRACT: This SuperSeries is composed of the following subset Series: GSE19309: Dkk4 and Eda regulate distinctive developmental mechanisms for subtypes of mouse hair-1 GSE19312: Dkk4 and Eda regulate distinctive developmental mechanisms for subtypes of mouse hair-2 Refer to individual Series

ORGANISM(S): Mus musculus

SUBMITTER: Minoru Ko

PROVIDER: E-GEOD-19364 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Dkk4 and Eda regulate distinctive developmental mechanisms for subtypes of mouse hair.

Cui Chang-Yi CY Kunisada Makoto M Piao Yulan Y Childress Victoria V Ko Minoru S H MS Schlessinger David D

PloS one 20100401 4

The mouse hair coat comprises protective "primary" and thermo-regulatory "secondary" hairs. Primary hair formation is ectodysplasin (Eda) dependent, but it has been puzzling that Tabby (Eda(-/y)) mice still make secondary hair. We report that Dickkopf 4 (Dkk4), a Wnt antagonist, affects an auxiliary pathway for Eda-independent development of secondary hair. A Dkk4 transgene in wild-type mice had no effect on primary hair, but secondary hairs were severely malformed. Dkk4 action on secondary hair ...[more]

PMID: 20386733

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Project description:Sweat glands play a fundamental role in thermal regulation in man, but the molecular mechanism of their development remains unknown. To initiate analyses, we compared the model of Eda mutant Tabby mice, in which sweat glands were not formed, to wild-type mice. We inferred developmental stages and critical genes based on observations at 7 time points spanning embryonic, postnatal and adult life. In wild-type footpads, sweat gland germs were detected at E17.5. The coiling of secretory portions started at postnatal day 1 (P1), and sweat gland formation was essentially complete by P5. Consistent with a controlled morphological progression, expression profiling revealed stage-specific gene expression changes. Similar to the development of hair follicles the other major skin appendage controlled by EDA sweat gland induction and initial progression was accompanied by Eda-dependent up-regulation of the Shh pathway. During the further development of sweat gland secretory portions, Foxa1 and Foxi1, not at all expressed in hair follicles, were progressively up-regulated in wild-type but not in Tabby footpads. Upon completion of wild-type development, Shh declined to Tabby levels, but Fox family genes remained at elevated levels in mature sweat glands. The results provide a framework for the further analysis of phased downstream regulation of gene action, possibly by a signaling cascade, in response to Eda. This SuperSeries is composed of the following subset Series: GSE14870: Requirement for Shh and Fox family genes at different stages in sweat gland development (E15.5) GSE14871: Requirement for Shh and Fox family genes at different stages in sweat gland development (E16.5) GSE14872: Requirement for Shh and Fox family genes at different stages in sweat gland development (E17.5) GSE14873: Requirement for Shh and Fox family genes at different stages in sweat gland development (P1) GSE14874: Requirement for Shh and Fox family genes at different stages in sweat gland development (P3) GSE14876: Requirement for Shh and Fox family genes at different stages in sweat gland development (P5) GSE14877: Requirement for Shh and Fox family genes at different stages in sweat gland development (Adult) To define target genes of Eda during sweat gland development, we carried out microarray experiments with mouse footpads that from 7 developmental time points including E15.5, E16.5, E17.5, P1, P3, P5 and 8 weeks of wild-type and Tabby mice. Refer to individual Series

Project description:Nails protect the soft tissue of the tips of digits in humans. In birds and mammals the equivalent claws are used for purposes including capturing prey, digging, climbing, fighting and maintaining dexterity and balance. The molecular mechanism of nail (and claw) development is largely unknown, but we have recently identified a Wnt receptor gene, Frizzled6 (Fzd6), as mutated in a human autosomal-recessive nail dysplasia. To investigate the action of Fzd6 in claw development at the molecular level, we compared gene expression profiles of digit tips of wild-type and Fzd6-/- mice, and show that Fzd6 regulates the transcription of a striking number of epidermal differentiation-related genes. Sixty-three genes encoding keratins, keratin associated proteins, and transglutaminases and their substrates were significantly down-regulated in the knockout mice. Among them, four hard keratins, Krt86, Krt81, Krt34 and Krt31; two epithelial keratins, Krt6a and Krt6b; and transglutaminase1 were known to be expressed in nails and involved in nail abnormality when dysregulated. Immunohistochemical studies revealed decreased expression of Krt86, Krt6b and involucrin in the epidermal portion of the claw field in the knockout embryos. We further show that Dkk4, a Wnt antagonist, was significantly down-regulated in Fzd6-/- mice along with Wnt, Bmp and Hh family genes; and Dkk4 transgenic mice showed a subtly but appreciably modified claw phenotype. Thus, Fzd6-mediated Wnt signaling likely regulates the overall differentiation process of nail/claw formation. Heterozygous Fzd6+/- mice (kindly provided by Dr. J. Nathans) were crossed to generate Fzd6+/-, Fzd6-/- and wild-type offspring. Timed matings were set up to harvest embryos at E14.5, E16.5 and E18.5. The morning after mating was designated as E0.5. Tails and the digital tips from forelimbs of three wild-type and Fzd6-/- mice from each embryonic time-point were excised, immediately frozen on dry ice, and stored at 80 C freezer until use. Genotyping was done as described previously (15). RNA was extracted using Trizol Reagent (Life technologies). RNA from dissected forelimbs from each embryo of the three time-points was used for microarray analysis.

Dataset Information

Dkk4 and Eda regulate distinctive developmental mechanisms for subtypes of mouse hair

Publications

Dkk4 and Eda regulate distinctive developmental mechanisms for subtypes of mouse hair.

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