Identification of Multiple Subsets of Ventral Interneurons and Differential Distribution along the Rostrocaudal Axis of the Developing Spinal Cord

Abstract

The spinal cord contains neuronal circuits termed Central Pattern Generators (CPGs) that coordinate rhythmic motor activities. CPG circuits consist of motor neurons and multiple interneuron cell types, many of which are derived from four distinct cardinal classes of ventral interneurons, called V0, V1, V2 and V3. While significant progress has been made on elucidating the molecular and genetic mechanisms that control ventral interneuron differentiation, little is known about their distribution along the antero-posterior axis of the spinal cord and their diversification. Here, we report that V0, V1 and V2 interneurons exhibit distinct organizational patterns at brachial, thoracic and lumbar levels of the developing spinal cord. In addition, we demonstrate that each cardinal class of ventral interneurons can be subdivided into several subsets according to the combinatorial expression of different sets of transcription factors, and that these subsets are differentially distributed along the rostrocaudal axis of the spinal cord. This comprehensive molecular profiling of ventral interneurons provides an important resource for investigating neuronal diversification in the developing spinal cord and for understanding the contribution of specific interneuron subsets on CPG circuits and motor control.

Prdm12 specifies V1 interneurons through cross-repressive interactions with Dbx1 and Nkx6 genes in Xenopus

“…In the mouse, V1 INs play an important role in locomotion (Gosgnach et al, 2006;Zhang et al, 2014). Our Prdm12 knockdown experiments indicate that the aINs, the homologues of V1 INs, are required for swimming movement in Xenopus, as observed for CiA INs in zebrafish (Zannino et al, 2014).…”

“…In aquatic vertebrates, this class of INs comprises only one type of multifunctional INs, known as circumferential ipsilateral ascending neurons (CiA) in fish and ascending interneurons (aINs) in frogs. In mammals, the V1 class of INs that plays a crucial role in regulating the rhythm of locomotor outputs and flexor-extensor inhibition (Gosgnach et al, 2006;Zhang et al, 2014) comprises a large variety of derivatives, including Renshaw cells (RCs) and putative reciprocal Ia inhibitory INs (Ia INs) (Alvarez et al, 2005;Siembab et al, 2010;BenitoGonzalez and Alvarez, 2012;Francius et al, 2013). In the chick, the population of En1-expressing neurons in the embryonic spinal cord has equally been shown to be heterogeneous (Wenner et al, 2000).…”

Commissural axonal corridors instruct neuronal migration in the mouse spinal cord

“…1) 22,27 . We examined the migration of cell bodies from both predominantly commissurally projecting neurons, V0 and V3 neurons, and V2a and V2c neurons, which are likely to be ipsilaterally projecting populations [28][29][30][31][32][33] . The nuclear position of these neuronal subpopulations were identified by transcription factor labelling, V0v/V0cg referred to in text as V0 (Evx1/2 þ ), V2a (Chx10 þ ), V2c (Sox1 þ ) and V3 (Nkx2.2 þ ) neurons 21 .…”

“…6) 32,40 . This suggests the general relationship between commissural axons and V3 neurons may be preserved between mouse and chicken embryos.…”

The late and dual origin of cerebrospinal fluid-contacting neurons in the mouse spinal cord

“…In the ventral neural tube, graded sonic hedgehog signaling activates transcriptional regulatory networks responsible for the interpretation of inductive signals and the subdivision of the neuroepithelium into five neural progenitor domains (designated pMN and p0-p3) (Briscoe et al, 2000;Balaskas et al, 2012;Lek et al, 2010). These dorsoventrally restricted progenitors produce distinct corresponding early-born classes of postmitotic neurons (motoneurons and V0-V3 interneurons) identified by the expression of specific sets of transcription factors (Jessell, 2000;Briscoe and Novitch, 2008;Goulding, 2009;Francius et al, 2013). As an example of further neuronal diversification, p2 progenitors generate several types of V2 interneurons, including excitatory V2a and V2d neurons, inhibitory V2b interneurons, which express the transcription factors Gata2 and Gata3, and V2c cells (Karunaratne et al, 2002;Li et al, 2005;Peng et al, 2007;Panayi et al, 2010;Panayiotou et al, 2013;Dougherty et al, 2013).…”