Making sense out of spinal cord somatosensory development

Abstract

The spinal cord integrates and relays somatosensory input, leading to complex motor responses. Research over the past couple of decades has identified transcription factor networks that function during development to define and instruct the generation of diverse neuronal populations within the spinal cord. A number of studies have now started to connect these developmentally defined populations with their roles in somatosensory circuits. Here, we review our current understanding of how neuronal diversity in the dorsal spinal cord is generated and we discuss the logic underlying how these neurons form the basis of somatosensory circuits.

Sonic hedgehog in vertebrate neural tube development

“…Thus, in the ventral half of the spinal cord, motor neurons and interneurons are formed. Analogous transcriptional codes are found in other regions of the neural tube and underlie the spatial pattern of neurogenesis in the dorsal half of the spinal cord (reviewed in Lai et al, 2016) and in the brain (for reviews see (Guillemot, 2007;Pearson and Placzek, 2013;Scholpp and Lumsden, 2010). This principle, in which the spatially restricted expression of transcription factors in neural progenitors results in the spatially segregated generation of distinct neuronal subtypes, is the first step in the assembly of functional neuronal circuits.…”

Gene, cell, and organ multiplication drives inner ear evolution

“…Most dorsal in either is the expression of Atoh1, Neurog1/2 and Ascl1 (Bermingham et al, 2001; Fritzsch et al, 2006b) with Neurog1/2 being only transiently expressed. However, more recent data show subdivisions in these populations through the nested expression of various transcription factors that likely are driven by the intricate pattern generated by ventralizing Shh signal emitted from the floor plate and the dorsalizing Wnt/BMP signal emitted from the roof plate (Fritzsch et al, 2006b; Lai et al, 2016). The basic pattern of bHLH genes is supplemented by addition of other bHLH and homeobox factors (Hernandez-Miranda et al, 2016) and shows local, rhombomere-specific variation in the hindbrain.…”

“…Formation of new nuclei is more likely to reflect assembly of novel interactions of the increasingly complex transcriptional landscape of the hindbrain that drives both expansion of cell populations through proliferation regulation and acquisition of novel phenotypes by regulatory changes of already complicated GRNs that evolved in the spinal cord to guide sophisticated, yet different, cell assemblies (Lai et al, 2016). In this context it is remarkable that some molecular conservation exists in peripheral pain receptors in skin and ear [Piezo1,2 (Wu et al, 2016)] and that loud sound causes pain sensation comparable to the pain perceived in the spinal cord.…”

Spiral Ganglion Neuron Projection Development to the Hindbrain in Mice Lacking Peripheral and/or Central Target Differentiation

“…Segregation of projections appears to develop before peripheral and central target cells differentiate (Zecca et al, 2015), suggesting that topological projections to the hindbrain arise through temporal progression of afferent development (Fritzsch et al, 2005a) or using existing diffusible factors such as Wnt's, Bmp's, and Shh that form dorso-ventral gradients (Litingtung and Chiang, 2000; Fritzsch et al, 2006; Lai et al, 2016). The mammalian vestibular afferents develop about 2 days before cochlear afferents and each projects without any apparent overlap directly to their future target nuclei (Fritzsch et al, 2015) around the time the first neurons exit the cell cycle (Pierce, 1967; Altman and Bayer, 1980).…”