RESEARCH ARTICLE Facial whisker pattern is not sufficient to instruct a whisker-related topographic map in the mouse somatosensory brainstem Christophe Laumonnerie 1, * , ‡ , Ahmad Bechara 1, ‡ , Nathalie Vilain 1 , Yukiko Kurihara 2,3 , Hiroki Kurihara 2,3 and Filippo M. Rijli 1,4,§ ABSTRACT Facial somatosensory input is relayed by trigeminal ganglion (TG) neurons and serially wired to brainstem, thalamus and cortex. Spatially ordered sets of target neurons generate central topographic maps reproducing the spatial arrangement of peripheral facial receptors. Facial pattern provides a necessary template for map formation, but may be insufficient to impose a brain somatotopic pattern. In mice, lower jaw sensory information is relayed by the trigeminal nerve mandibular branch, whose axons target the brainstem dorsal principal sensory trigeminal nucleus (dPrV). Input from mystacial whiskers is relayed by the maxillary branch and forms a topographic representation of rows and whiskers in the ventral PrV (vPrV). To investigate peripheral organisation in imposing a brain topographic pattern, we analysed Edn1 -/- mice, which present ectopic whisker rows on the lower jaw. We found that these whiskers were innervated by mandibular TG neurons which initially targeted dPrV. Unlike maxillary TG neurons, the ectopic whisker-innervating mandibular neuron cell bodies and pre-target central axons did not segregate into a row-specific pattern nor target the dPrV with a topographic pattern. Following periphery-driven molecular repatterning to a maxillary-like identity, mandibular neurons partially redirected their central projections from dPrV to vPrV. Thus, while able to induce maxillary- like molecular features resulting in vPrV final targeting, a spatially ordered lower jaw ectopic whisker pattern is insufficient to impose row-specific pre-target organisation of the central mandibular tract or a whisker-related matching pattern of afferents in dPrV. These results provide novel insights into periphery-dependent versus periphery- independent mechanisms of trigeminal ganglion and brainstem patterning in matching whisker topography. KEY WORDS: Whisker-related barrelette map, Mandibular brainstem representation, Topographic map, Hindbrain, Trigeminal ganglion, Trigeminal somatotopy, Edn1, Cdh13, Tbx3, Hmx1 INTRODUCTION Relay of somatosensory stimuli from the body surface to higher brain centres is highly organised, allowing the sensing of positional origin of an input. Facial somatosensory inputs are serially relayed through the trigeminal circuit to the brainstem, thalamus and neocortex. The trigeminal circuit is somatotopically organised, such that topographic maps of connectivity matching the distribution and density of sensory receptors of facial dermatomes are generated at all levels of the pathway (Erzurumlu and Killackey, 1983; Erzurumlu et al., 2010; Ma, 1991, 1993; Ma and Woolsey, 1984; Schlaggar and O’Leary, 1993; Van Der Loos, 1976; Woolsey and Van der Loos, 1970). Distinct facial dermatomes are innervated by the peripheral axonal processes of trigeminal ganglion (TG) primary sensory neurons, whose central axons form the trigeminal nerve (nV) and project to innervate second order neurons in the brainstem trigeminal column, composed of the rostral principal (PrV) and the caudal spinal (SpV) sensory nuclei. TG neurons bridge the facial sensory periphery and the brainstem where facial maps are first formed. During prenatal development, somatotopic segregation of TG cell bodies contributes to the segregation of the trigeminal nerve into its three main divisions – the mandibular, maxillary and ophtalmic branches, which peripherally innervate the corresponding facial dermatomes (Arvidsson and Rice, 1991; Erzurumlu and Jhaveri, 1992; Erzurumlu and Killackey, 1983; Erzurumlu et al., 2010; Hodge et al., 2007). In mouse, the largest portion of the facial somatosensory map is devoted to the representation of mystacial whiskers which are organised into five rows of four to seven follicles at invariant positions on the snout. Whisker inputs are somatotopically mapped at each level of the pathway as spatially ordered neuronal modules, called barrelettes (brainstem), barreloids (thalamus), and barrels (cortex) (Ma and Woolsey, 1984; Van Der Loos, 1976; Woolsey and Van der Loos, 1970), reproducing facial whisker distribution. The central axons of the mouse trigeminal nerve divisions start sending radially oriented collaterals at about embryonic day (E) 14.5 to innervate the PrV and SpV brainstem nuclei, and at about E16.5 begin to arborise, forming dense terminals (Erzurumlu et al., 2006; Ozdinler and Erzurumlu, 2002). In the developing PrV, mandibular axon collaterals selectively target the dorsal portion (dPrV) whereas whisker-related afferent collaterals preferentially target the ventral portion (vPrV) with a dorsoventral row-specific organisation (Erzurumlu and Killackey, 1983; Erzurumlu et al., 2010; Hodge et al., 2007; Oury et al., 2006; Xiang et al., 2010; this study). Thus, the spatial segregation of collateral targeting by distinct trigeminal divisions in PrV provides an early template to build topographic equivalence between the face and the brainstem. To what extent peripheral signals and/or patterns are sufficient to impose a central somatotopic pattern is still debated. One approach to understanding a potential instructive role of the periphery in imposing a central somatotopic pattern has been to manipulate the number and/or spatial organisation of whiskers within the whisker pad. Such peripheral changes were reflected on the somatotopy of the barrel map (Ohsaki et al., 2002; Van der Loos et al., 1984). Moreover, retrograde signalling from the developing face was shown to be involved in establishing spatial patterns of gene Received 21 July 2015; Accepted 15 September 2015 1 Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, Basel 4058, Switzerland. 2 Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8654, Japan. 3 Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST), Chiyoda- ku, Tokyo, 102-0075, Japan. 4 University of Basel, Basel 4056, Switzerland. *Present address: St. Jude Children’s Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA. ‡ These authors contributed equally to this work § Author for correspondence (filippo.rijli@fmi.ch) 3704 © 2015. Published by The Company of Biologists Ltd | Development (2015) 142, 3704-3712 doi:10.1242/dev.128736 DEVELOPMENT