Mesodermal and neuronal retinoids regulate the induction and maintenance of limb innervating spinal motor neurons |
| |
Authors: | Ji Sheng-Jian Zhuang BinQuan Falco Crystal Schneider André Schuster-Gossler Karin Gossler Achim Sockanathan Shanthini |
| |
Institution: | a Department of Neuroscience, Johns Hopkins University School of Medicine, 725 N Wolfe Street, Baltimore, MD 21205, USA b Institute for Molecular Biology OE5250, Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany |
| |
Abstract: | During embryonic development, the generation, diversification and maintenance of spinal motor neurons depend upon extrinsic signals that are tightly regulated. Retinoic acid (RA) is necessary for specifying the fates of forelimb-innervating motor neurons of the Lateral Motor Column (LMC), and the specification of LMC neurons into medial and lateral subtypes. Previous studies implicate motor neurons as the relevant source of RA for specifying lateral LMC fates at forelimb levels. However, at the time of LMC diversification, a significant amount of retinoids in the spinal cord originates from the adjacent paraxial mesoderm. Here we employ mouse genetics to show that RA derived from the paraxial mesoderm is required for lateral LMC induction at forelimb and hindlimb levels, demonstrating that mesodermally synthesized RA functions as a second source of signals to specify lateral LMC identity. Furthermore, reduced RA levels in postmitotic motor neurons result in a decrease of medial and lateral LMC neurons, and abnormal axonal projections in the limb; invoking additional roles for neuronally synthesized RA in motor neuron maintenance and survival. These findings suggest that during embryogenesis, mesodermal and neuronal retinoids act coordinately to establish and maintain appropriate cohorts of spinal motor neurons that innervate target muscles in the limb. |
| |
Keywords: | Retinoids Motor neuron Specification Maintenance |
本文献已被 ScienceDirect PubMed 等数据库收录! |
|