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Mammalian BarH1 confers commissural neuron identity on dorsal cells in the spinal cord.

ABSTRACT: Commissural neurons in the spinal cord project their axons through the floor plate using a number of molecular interactions, such as netrins and their receptor DCC (deleted in colorectal cancer). However, the molecular cascades that control differentiation of commissural neurons are less characterized. A homeobox gene, MBH1 (mammalian BarH1) was expressed specifically in a subset of dorsal cells in the developing spinal cord. Transgenic mice that carried lacZ and MBH1-flanking genome sequences demonstrated that MBH1 was expressed by commissural neurons. To analyze the function of MBH1, we established an in vivo electroporation method for the transfer of DNA into the mouse spinal cord. Ectopic expression of MBH1 drove dorsal cells into the fate of commissural neurons with concomitant expression of TAG-1 (transiently expressed axonal surface glycoprotein 1) and DCC. Cells ectopically expressing MBH1 migrated to the deep dorsal horn, in which endogenous MBH1-positive cells accumulated. These results suggest that MBH1 functions upstream of TAG-1 and DCC and is involved in the fate determination of commissural neurons in the spinal cord.

SUBMITTER: Saba R

PROVIDER: S-EPMC6742033 | biostudies-literature | 2003 Mar

REPOSITORIES: biostudies-literature

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Mammalian BarH1 confers commissural neuron identity on dorsal cells in the spinal cord.

Saba Rie R Nakatsuji Norio N Saito Tetsuichiro T

The Journal of neuroscience : the official journal of the Society for Neuroscience 20030301 6

Commissural neurons in the spinal cord project their axons through the floor plate using a number of molecular interactions, such as netrins and their receptor DCC (deleted in colorectal cancer). However, the molecular cascades that control differentiation of commissural neurons are less characterized. A homeobox gene, MBH1 (mammalian BarH1) was expressed specifically in a subset of dorsal cells in the developing spinal cord. Transgenic mice that carried lacZ and MBH1-flanking genome sequences d ...[more]

PMID: 12657654

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Project description:The neuron-intrinsic response to axonal injury differs markedly between neurons of the peripheral and central nervous system. Following a peripheral lesion, a robust axonal growth program is initiated, whereas neurons of the central nervous system do not mount an effective regenerative response. Increasing the neuron-intrinsic regenerative response would therefore be one way to promote axonal regeneration in the injured central nervous system. The large-diameter sensory neurons located in the dorsal root ganglia are pseudo-unipolar neurons that project one axon branch into the spinal cord, and, via the dorsal column to the brain stem, and a peripheral process to the muscles and skin. Dorsal root ganglion neurons are ideally suited to study the neuron-intrinsic injury response because they exhibit a successful growth response following peripheral axotomy, while they fail to do so after a lesion of the central branch in the dorsal column. The dorsal column injury model allows the neuron-intrinsic regeneration response to be studied in the context of a spinal cord injury. Here we will discuss the advantages and disadvantages of this model. We describe the surgical methods used to implement a lesion of the ascending fibers, the anatomy of the sensory afferent pathways and anatomical, electrophysiological, and behavioral techniques to quantify regeneration and functional recovery. Subsequently we review the results of experimental interventions in the dorsal column lesion model, with an emphasis on the molecular mechanisms that govern the neuron-intrinsic injury response and manipulations of these after central axotomy. Finally, we highlight a number of recent advances that will have an impact on the design of future studies in this spinal cord injury model, including the continued development of adeno-associated viral vectors likely to improve the genetic manipulation of dorsal root ganglion neurons and the use of tissue clearing techniques enabling 3D reconstruction of regenerating axon tracts. © 2018 The Authors. Developmental Neurobiology Published by Wiley Periodicals, Inc. Develop Neurobiol 00: 000-000, 2018.

Dataset Information

Mammalian BarH1 confers commissural neuron identity on dorsal cells in the spinal cord.

Publications

Mammalian BarH1 confers commissural neuron identity on dorsal cells in the spinal cord.

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