A regulatory network involving Foxn4, Mash1 and delta-like 4/Notch1 generates V2a and V2b spinal interneurons from a common progenitor pool.

In the developing central nervous system, cellular diversity depends in part on organising signals that establish regionally restricted progenitor domains, each of which produces distinct types of differentiated neurons. However, the mechanisms of neuronal subtype specification within each progenitor domain remain poorly understood. The p2 progenitor domain in the ventral spinal cord gives rise to two interneuron (IN) subtypes, V2a and V2b, which integrate into local neuronal networks that control motor activity and locomotion. Foxn4, a forkhead transcription factor, is expressed in the common progenitors of V2a and V2b INs and is required directly for V2b but not for V2a development. We show here in experiments conducted using mouse and chick that Foxn4 induces expression of delta-like 4 (Dll4) and Mash1 (Ascl1). Dll4 then signals through Notch1 to subdivide the p2 progenitor pool. Foxn4, Mash1 and activated Notch1 trigger the genetic cascade leading to V2b INs, whereas the complementary set of progenitors, without active Notch1, generates V2a INs. Thus, Foxn4 plays a dual role in V2 IN development: (1) by initiating Notch-Delta signalling, it introduces the asymmetry required for development of V2a and V2b INs from their common progenitors; (2) it simultaneously activates the V2b genetic programme.

Unilateral spinal nerve ligation leads to an asymmetrical distribution of mast cells in the thalamus of female but not male mice.

Mast cells are restricted to the leptomeninges and thalamus of healthy mice. These populations are increased by stress and highly sensitive to reproductive hormones. To examine the influence of nociception, a form of stress, on thalamic mast cells, we ligated the left fifth lumbar spinal nerve of male and female mice to induce hyperalgesia. Two, 7 and 14 days later, mice were killed and thalami examined histologically using toluidine blue stain. The total number of thalamic mast cells was not influenced by ligation of the spinal nerve compared to sham-operation in either female or male mice. However, in females, the percent of thalamic mast cells located on the side of the thalamus contralateral to the ligation was greater on days 2 and 7, coincident with mechanical hyperalgesia. At these times, areas in which mast cells were most dense contralateral to nerve-injury included the posterior (Po) and lateral geniculate (LG) nuclei compared to their symmetrical distribution in sham-operated mice. These data suggest that local nociceptive signals to each side of the thalamus rather than stress hormones influence the location of mast cells during the development of allodynia and hyperalgesia. In addition, both hyperalgesia and mast cell distribution induced by nerve-ligation differ in females compared to males, reflecting a novel neuroimmune response to pain within the CNS.

Ascending projections from the area around the spinal cord central canal: A Phaseolus vulgaris leucoagglutinin study in rats.

A single small iontophoretic injection of Phaseolus vulgaris leucoagglutinin labels projections from the area surrounding the spinal cord central canal at midthoracic (T6-T9) or lumbosacral (L6-S1) segments of the spinal cord. The projections from the midthoracic or lumbosacral level of the medial spinal cord are found: 1) ascending ipsilaterally in the dorsal column near the dorsal intermediate septum or the midline of the gracile fasciculus, respectively; 2) terminating primarily in the dorsal, lateral rim of the gracile nucleus and the medial rim of the cuneate nucleus or the dorsomedial rim of the gracile nucleus, respectively; and 3) ascending bilaterally with slight contralateral predominance in the ventrolateral quadrant of the spinal cord and terminating in the ventral and medial medullary reticular formation. Other less dense projections are to the pons, midbrain, thalamus, hypothalamus, and other forebrain structures. Projections arising from the lumbosacral level are also found in Barrington's nucleus. The results of the present study support previous retrograde tract tracing and physiological studies from our group demonstrating that the neurons in the area adjacent to the central canal of the midthoracic or lumbosacral level of the spinal cord send long ascending projections to the dorsal column nucleus that are important in the transmission of second-order afferent information for visceral nociception. Thus, the axonal projections through both the dorsal and the ventrolateral white matter from the CC region terminate in many regions of the brain providing spinal input for sensory integration, autonomic regulation, motor and emotional responses, and limbic activation.