The Temporal Contribution of the Gbx2 Lineage to Cerebellar Neurons

The cerebellum (Cb) is an exquisite structure that controls elaborate motor behaviors and is essential for sensory-motor learning. During development, the Cb is derived from rhombomere 1 (r1). Within this embryonic compartment, precursors in r1 are patterned by signaling cues originating from the is...

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Main Authors: Nellwyn Hagan, Juliana Guarente, Debra Ellisor, Mark Zervas
Format: Article
Language:English
Published: Frontiers Media S.A. 2017-07-01
Series:Frontiers in Neuroanatomy
Subjects:
Online Access:http://journal.frontiersin.org/article/10.3389/fnana.2017.00050/full
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author Nellwyn Hagan
Juliana Guarente
Debra Ellisor
Mark Zervas
Mark Zervas
Mark Zervas
author_facet Nellwyn Hagan
Juliana Guarente
Debra Ellisor
Mark Zervas
Mark Zervas
Mark Zervas
author_sort Nellwyn Hagan
collection DOAJ
description The cerebellum (Cb) is an exquisite structure that controls elaborate motor behaviors and is essential for sensory-motor learning. During development, the Cb is derived from rhombomere 1 (r1). Within this embryonic compartment, precursors in r1 are patterned by signaling cues originating from the isthmus organizer (IsO) and subsequently undergo complex morphogenic movements to establish their final position in the mature Cb. The transcription factor Gbx2 is expressed in the developing Cb and is intimately involved in organizing and patterning the Cb. Nevertheless, how precursors expressing Gbx2 at specific embryonic time points contribute to distinct cell types in the adult Cb is unresolved. In this study, we used Genetic Inducible Fate Mapping (GIFM) to mark Gbx2-expressing precursors with fine temporal resolution and to subsequently track this lineage through embryogenesis. We then determined the terminal neuronal fate of the Gbx2 lineage in the adult Cb. Our analysis demonstrates that the Gbx2 lineage contributes to the Cb with marking over the course of five stages: Embryonic day 7.5 (E7.5) through E11.5. The Gbx2 lineage gives rise to Purkinje cells, granule neurons, and deep cerebellar neurons across these marking stages. Notably, the contribution of the Gbx2 lineage shifts as development proceeds with each marking stage producing a distinct profile of mature neurons in the adult Cb. These findings demonstrate the relationship between the temporal expression of Gbx2 and the terminal cell fate of neurons in the Cb. Based on these results, Gbx2 is critical to Cb development, not only for its well-defined role in positioning and maintaining the IsO, but also for guiding the development of Cb precursors and determining the identity of Cb neurons.
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spelling doaj.art-fc81cde9450842ce95207107ca4843022022-12-22T00:50:44ZengFrontiers Media S.A.Frontiers in Neuroanatomy1662-51292017-07-011110.3389/fnana.2017.00050269338The Temporal Contribution of the Gbx2 Lineage to Cerebellar NeuronsNellwyn Hagan0Juliana Guarente1Debra Ellisor2Mark Zervas3Mark Zervas4Mark Zervas5Division of Biology and Medicine, Department of Neuroscience, Brown UniversityProvidence, RI, United StatesDivision of Biology and Medicine, Department of Molecular Biology, Cell Biology and Biochemistry, Brown UniversityProvidence, RI, United StatesDivision of Biology and Medicine, Department of Molecular Biology, Cell Biology and Biochemistry, Brown UniversityProvidence, RI, United StatesDivision of Biology and Medicine, Department of Neuroscience, Brown UniversityProvidence, RI, United StatesDivision of Biology and Medicine, Department of Molecular Biology, Cell Biology and Biochemistry, Brown UniversityProvidence, RI, United StatesDepartment of Neuroscience, AmgenCambridge, MA, United StatesThe cerebellum (Cb) is an exquisite structure that controls elaborate motor behaviors and is essential for sensory-motor learning. During development, the Cb is derived from rhombomere 1 (r1). Within this embryonic compartment, precursors in r1 are patterned by signaling cues originating from the isthmus organizer (IsO) and subsequently undergo complex morphogenic movements to establish their final position in the mature Cb. The transcription factor Gbx2 is expressed in the developing Cb and is intimately involved in organizing and patterning the Cb. Nevertheless, how precursors expressing Gbx2 at specific embryonic time points contribute to distinct cell types in the adult Cb is unresolved. In this study, we used Genetic Inducible Fate Mapping (GIFM) to mark Gbx2-expressing precursors with fine temporal resolution and to subsequently track this lineage through embryogenesis. We then determined the terminal neuronal fate of the Gbx2 lineage in the adult Cb. Our analysis demonstrates that the Gbx2 lineage contributes to the Cb with marking over the course of five stages: Embryonic day 7.5 (E7.5) through E11.5. The Gbx2 lineage gives rise to Purkinje cells, granule neurons, and deep cerebellar neurons across these marking stages. Notably, the contribution of the Gbx2 lineage shifts as development proceeds with each marking stage producing a distinct profile of mature neurons in the adult Cb. These findings demonstrate the relationship between the temporal expression of Gbx2 and the terminal cell fate of neurons in the Cb. Based on these results, Gbx2 is critical to Cb development, not only for its well-defined role in positioning and maintaining the IsO, but also for guiding the development of Cb precursors and determining the identity of Cb neurons.http://journal.frontiersin.org/article/10.3389/fnana.2017.00050/fullGenetic Inducible Fate Mapping (GIFM)Gbx2cell fate decisionscerebellumPurkinje cellsgranule neurons
spellingShingle Nellwyn Hagan
Juliana Guarente
Debra Ellisor
Mark Zervas
Mark Zervas
Mark Zervas
The Temporal Contribution of the Gbx2 Lineage to Cerebellar Neurons
Frontiers in Neuroanatomy
Genetic Inducible Fate Mapping (GIFM)
Gbx2
cell fate decisions
cerebellum
Purkinje cells
granule neurons
title The Temporal Contribution of the Gbx2 Lineage to Cerebellar Neurons
title_full The Temporal Contribution of the Gbx2 Lineage to Cerebellar Neurons
title_fullStr The Temporal Contribution of the Gbx2 Lineage to Cerebellar Neurons
title_full_unstemmed The Temporal Contribution of the Gbx2 Lineage to Cerebellar Neurons
title_short The Temporal Contribution of the Gbx2 Lineage to Cerebellar Neurons
title_sort temporal contribution of the gbx2 lineage to cerebellar neurons
topic Genetic Inducible Fate Mapping (GIFM)
Gbx2
cell fate decisions
cerebellum
Purkinje cells
granule neurons
url http://journal.frontiersin.org/article/10.3389/fnana.2017.00050/full
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