, 2010). How is diversity engendered in developing motor neurons? All motor

neurons initially derive from ventral progenitor cells that are specified to become Olig2+ motor neuron progenitors through shh and retinoic acid (RA) signals (Novitch et al., 2003 and Diez del Corral et al., 2003). Postmitotic motor neuron generation from Olig2+ progenitors is governed by RA through the induction of GDE2, a six-transmembrane protein with an extracellular glycerophosphodiester phosphodiesterase Selleck PD-1/PD-L1 inhibitor (GDPD) domain (Novitch et al., 2003, Diez del Corral et al., 2003, Rao and Sockanathan, 2005, Yan et al., 2009 and Nogusa et al., 2004). GDE2 is expressed in all somatic motor neurons and synchronizes neurogenic and motor neuron fate specification pathways to drive motor neuron generation through extracellular GDPD activity (Rao and Sockanathan, 2005 and Yan et al., 2009). Newly generated motor neurons share generic motor neuron properties that are distinct from neighboring interneurons, such as their use of acetylcholine as a neurotransmitter

and the ability of their axons to exit the ventral root. Postmitotic motor neurons subsequently check details diversify into different motor columns and pools that have distinct positional, molecular, and axonal projection profiles that are fundamental to motor circuit formation (Dasen and Jessell, 2009). The major motor columns in the spinal cord consist of the median motor column (MMC), which spans the entire body axis and innervates dorsal axial muscles; the preganglionic

columns (PGCs) and hypaxial motor columns (HMCs), located primarily at thoracic levels, which respectively target the viscera and body wall muscles (Prasad and Hollyday, 1991); and the limb-specific lateral motor columns (LMCs), which are divided into lateral and medial subdivisions that innervate dorsal and ventral limb musculature (Landmesser, 1978 and Landmesser, 2001). Medial and lateral LMC motor neurons are further clustered into motor pools according to their projections to individual target muscles (Gutman et al., 1993, Landmesser, 1978 and Lin ALOX15 et al., 1998). Current models propose that columnar and pool identities are instructed in newly born motor neurons via intrinsic hierarchical transcription programs and extrinsic signals. The distinction between MMC and non-MMC motor columns is imposed via ventrally derived Wnt signals (Agalliu et al., 2009), while non-MMC motor columnar identity is directed by early mesodermal sources of graded FGF, retinoid, and TGF β∼-like signals. These pathways ultimately regulate the motor-neuron-specific expression of Hox transcription factors in restricted rostral-caudal domains, where they regulate the expression of transcription factors such as the LIM homeodomain proteins to specify the settling position and axonal projection patterns of prospective LMC and PGC neurons (Dasen and Jessell, 2009, Ji et al., 2009, Shah et al.