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

Abstract

AbstractWhiskers (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,Prdm1conditional 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 thatPrdm1is 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 ofBmp2, Shh, Bmp4, Krt17, Edar, Gli1though leaving the β-catenin driven first dermal signal intact. Furthermore, we prove thatPrdm1expressing 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 thatLef1acts upstream ofPrdm1and 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.