Mammalian-specific ectodermal enhancers control the expression of Hoxc genes in developing nails and hair follicles

Proceedings of the National Academy of Sciences of the United States of America
M. Fernandez-GuerreroM. A. Ros

Abstract

Vertebrate Hox genes are critical for the establishment of structures during the development of the main body axis. Subsequently, they play important roles either in organizing secondary axial structures such as the appendages, or during homeostasis in postnatal stages and adulthood. Here, we set up to analyze their elusive function in the ectodermal compartment, using the mouse limb bud as a model. We report that the HoxC gene cluster was co-opted to be transcribed in the distal limb ectoderm, where it is activated following the rule of temporal colinearity. These ectodermal cells subsequently produce various keratinized organs such as nails or claws. Accordingly, deletion of the HoxC cluster led to mice lacking nails (anonychia), a condition stronger than the previously reported loss of function of Hoxc13, which is the causative gene of the ectodermal dysplasia 9 (ECTD9) in human patients. We further identified two mammalian-specific ectodermal enhancers located upstream of the HoxC gene cluster, which together regulate Hoxc gene expression in the hair and nail ectodermal organs. Deletion of these regulatory elements alone or in combination revealed a strong quantitative component in the regulation of Hoxc genes in the ectode...Continue Reading

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Citations

Jan 19, 2021·Nature·Axel MeyerManfred Schartl
Jul 14, 2021·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Marc Fernandez-GuerreroMarian A Ros
Aug 20, 2021·Nature Communications·Christopher Chase BoltDenis Duboule
Oct 18, 2021·Experimental Dermatology·Carlos J PerezFernando Benavides

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Methods Mentioned

BETA
RNA-seq
PCA
transgenic
PCR
dissection

Software Mentioned

mVISTA
LAGAN
shuffle
mVISTA shuffle - LAGAN

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