Transcriptional Control of Interneuron Development in the Central NervousSystem.

Neurogenesis;Molecular;Cellular and Developmental Biology;Science;Neuroscience

Skaggs, Kathryn AnnTurner, David ;

University of Michigan

关键词: Neurogenesis;    Molecular;    Cellular and Developmental Biology;    Science;    Neuroscience;   

Others  :  https://deepblue.lib.umich.edu/bitstream/handle/2027.42/78977/kskaggs_1.pdf?sequence=1&isAllowed=y

瑞士|英语

来源: The Illinois Digital Environment for Access to Learning and Scholarship

【 摘 要 】

This work addresses the role of two transcription factors in generation of specific neuronal subtypes in the developing central nervous system (CNS): the bHLH transcription factor Bhlhb5 in spinal cord and the paired-like homeobox gene Pitx2 in spinal cord and hindbrain development.Neural circuits that control motor activities depend on spatially and temporally ordered generation of distinct classes of spinal interneurons whose genesis is poorly understood.The Olig-related transcription factor Bhlhb5 plays two central roles in this process.Bhlhb5 repressor activity acts downstream of retinoid signaling and homeodomain proteins to promote formation of dI6, V1, and V2 interneuron progenitors and their differentiated progeny.Bhlhb5 is required to organize the spatially-restricted expression of Notch ligands Jagged1, Dll1, and Dll4 that affect the formation of the interneuron populations adjacent to Bhlhb5+ cells and influence the global pattern of neuronal differentiation.Through these actions, Bhlhb5 helps transform spatial information established by morphogen signaling into local cell-cell interactions associated with Notch signaling that control the progression of neurogenesis and extend neuronal diversity within the developing spinal cord.Pitx2 is involved in the regulation of left-right asymmetry and development of numerous organs, including pituitary, eyes, teeth, palate, heart, and limbs.Pitx2 is expressed in forebrain, midbrain, hindbrain, and spinal cord during development, with pleiotropic neurotransmitter phenotypes and functions.In spinal cord, Pitx2 is expressed in a subset of V0 interneurons that can be further subdivided by neurotransmitter phenotype.In hindbrain, Pitx2 is expressed in a discrete set of neurons in ventral rhombomere 1 that are GABAergic and may participate in local regulatory circuits.In addition to contributing to the understanding of normal developmental processes, elucidation of roles of proteins like Bhlhb5 and Pitx2 can provide valuable direction for designing therapeutic treatments for devastating neurological diseases.Enthusiasm for stem cell research comes from the promise of pluripotent neural stem cells to generate the many types of neurons damaged or missing in disease.Thus, a better understanding of processes that recapitulate normal development can be vital for developing therapies that use neural stem cells for CNS regeneration and repair.