Whiskers (vibrissae) are miniaturized organs that are designed for tactile sensing. Extremely conserved among mammals, they underwent a reduction in primates and disappeared in the human lineage. Furthermore, whiskers are highly innervated and their mechanoceptors signal to the primary somatosensory cortex, where a column of neurons called “barrel” represents each of them. This structure, known as barrel cortex, occupies a large portion of the somatosensory cortex of the rodent brain. Strikingly, Prdm1 conditional knockout mice are one of the rare transgenic strains that do not develop whisker hair follicles while still displaying a pelage (Robertson et al. 2007). Here we show that Prdm1 is expressed early on during whisker development, more precisely in clusters of mesenchymal cells before placode formation. Its conditional knockout leads to the loss of expression of Bmp2, Shh, Bmp4, Krt17, Edar, Gli1 though leaving the β-catenin driven first dermal signal intact. Furthermore, we prove that Prdm1 expressing cells not only act as a signaling center but also as a multipotent progenitor population contributing to the formation of the dermal papilla, dermal sheath and pericytes of the vascular sinuses of vibrissae. We confirm by genetic ablation experiments that the absence of motile vibrissae (macro vibrissae) formation reverberates on the organization of nerve wiring in the mystacial pads and organization of the barrel cortex. We prove that Lef1 acts upstream of Prdm1 and identify a potential enhancer (named Leaf) that might be involved in the evolutionary process that led to the progressive reduction of snout size and vibrissae in primates.

Early mechanisms of whisker development: Prdm1 and its regulation in whisker development and evolutionary loss / P.G. Manti, F. Darbellay, M. Leleu, B. Moret, J. Cuennet, F. Droux, M. Stoudmann, G. Mancini, A. Hautier, Y. Barrandon. - (2021 Mar 12). [10.1101/2021.03.11.433122]

Early mechanisms of whisker development: Prdm1 and its regulation in whisker development and evolutionary loss

P.G. Manti
Primo
;
2021-03-12

Abstract

Whiskers (vibrissae) are miniaturized organs that are designed for tactile sensing. Extremely conserved among mammals, they underwent a reduction in primates and disappeared in the human lineage. Furthermore, whiskers are highly innervated and their mechanoceptors signal to the primary somatosensory cortex, where a column of neurons called “barrel” represents each of them. This structure, known as barrel cortex, occupies a large portion of the somatosensory cortex of the rodent brain. Strikingly, Prdm1 conditional knockout mice are one of the rare transgenic strains that do not develop whisker hair follicles while still displaying a pelage (Robertson et al. 2007). Here we show that Prdm1 is expressed early on during whisker development, more precisely in clusters of mesenchymal cells before placode formation. Its conditional knockout leads to the loss of expression of Bmp2, Shh, Bmp4, Krt17, Edar, Gli1 though leaving the β-catenin driven first dermal signal intact. Furthermore, we prove that Prdm1 expressing cells not only act as a signaling center but also as a multipotent progenitor population contributing to the formation of the dermal papilla, dermal sheath and pericytes of the vascular sinuses of vibrissae. We confirm by genetic ablation experiments that the absence of motile vibrissae (macro vibrissae) formation reverberates on the organization of nerve wiring in the mystacial pads and organization of the barrel cortex. We prove that Lef1 acts upstream of Prdm1 and identify a potential enhancer (named Leaf) that might be involved in the evolutionary process that led to the progressive reduction of snout size and vibrissae in primates.
Settore BIO/18 - Genetica
https://www.biorxiv.org/content/10.1101/2021.03.11.433122v1
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/937536
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