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Biology subjects

Jessell, T. M.

Publications and source records attributed to Jessell, T. M..

3 recordsLinked to original sources

Distinct anatomical and functional corticospinal inputs innervate different spinal neuron types

The corticospinal tract exerts its influence on movement through spinal neurons, which can be divided into types that exhibit distinct functions. However, it remains unknown whether these functional distinctions are reflected in the corticospinal inputs that different types of spinal neurons receive. Using rabies monosynaptic tracing from individual neuron types in the cervical cord and 3D histological reconstruction in mice, we discovered that different types receive inputs distinctly distributed across cortex, and aligned with cell type function. This included a distinct, sparse distribution of direct inputs from cortex onto motor neurons. Coupling rabies tracing with activity measurement during motor behavior revealed different interneuron types receive different input activity patterns, primarily due to the topographical distribution of the corticospinal neurons contacting them. Our results establish that different spinal neuron types get distinct anatomical and functional inputs from the cortex, and reveal functionally relevant homology to primate corticospinal organization.

neuroscience↗

Muscle-derived Cues are Required to Specify Proprioceptor Pool Identity

The formation of spinal sensory-motor circuits requires the diversification of proprioceptive sensory neurons (pSNs). During embryonic development, pSNs acquire molecular identities aligned with the limb muscle that they supply, but the extent of pSN "pool" diversity and how it is established are poorly understood. We find that the gene v-set transmembrane domain-2b (vstm2b) is preferentially expressed in pSN pools supplying dorsal limb muscle targets along the proximodistal extent of the limb. Genetic removal of muscle precursor cells from the developing limb greatly reduces the number of pSNs expressing vstm2b, demonstrating a requirement for limb muscle in specifying pSN pool identity. Comparison of dorsal and ventral muscle precursors identifies spatially restricted expression of the genes lumican (lum), decorin (dcn), and BMP binding endothelial regulator (bmper), demonstrating that dorsal and ventral muscle groups possess distinct molecular identities early in embryonic development. Together, these findings show that limb muscle is required for the specification of pSN pool identity and define early molecular correlates of dorsoventral muscle identity that are positioned to drive neuronal diversity.

developmental biology↗

Prospective isolation of mouse and human hematopoietic stem cells using Plexin domain containing 2

Numerous strategies exist to isolate hematopoietic stem cells (HSCs) using complex combinations of markers and flow cytometry. However, robust identification of HSCs using imaging techniques is substantially more challenging which has prompted the recent development of HSC reporter mice. To date, none of the molecules used in these reporters have been useful for human HSC identification. Here we report that PLXDC2 is a useful marker for both mouse and human HSCs. Using a green fluorescent protein (GFP) knock-in at the Plxdc2 locus in mice (hereafter denoted as Plxdc2-GFP), we showed that Plxdc2-GFP is highly expressed in HSCs with 1 in 2.8 Plxdc2-GFP+CD150+ cells giving long-term multi-lineage reconstitution in transplantation. Moreover, we developed a novel human PLXDC2 antibody and showed that human PLXDC2+ HSCs have stronger long-term multilineage reconstitution ability compared with PLXDC2- HSCs in a xenograft model. Thus, our study identifies PLXDC2 as a highly relevant molecule in HSC identification, potentially allowing greater purity and live in vivo tracking of these cells. SummaryTo date, few molecules are available for isolation of HSCs across species. The present study shows that PLXDC2 is a highly useful molecule for isolation of HSCs, which works across mouse and human.

cell biology↗